Induced chiroptical changes of a water-soluble cryptophane by encapsulation of guest molecules and counterion effects

Article abstract of DOI:10.1002/chem.200902740

We report the synthesis of the water-soluble cryptophanol derivative 1 and the study of the chiroptical properties of its two enantiomers (>99%ee) by polarimetry, electronic circular dichroism (ECD), and vibrational circular dichroism (VCD). We show that cryptophanol 1 exhibits unusual chiroptical properties in water under basic conditions (pH>12). For instance, the shapes of the ECD and VCD spectra of 1 in water were strongly dependent on the nature of the alkali metal ions (Li⁺, Na⁺, K⁺, Cs ⁺) surrounding the cryptophane and whether or not a guest molecule is present inside the cavity of the host. To the best of our knowledge, this is the first example in which the nature of these counterions governs the chiropti-cal properties of a host molecule. Moreover, specific ECD spectra were obtained depending on the size of the guest molecules. This makes 1 a good sensor for small neutral molecules in aqueous solvent. Finally, VCD experiments associated with DFT calculations show that the chiroptical changes can be directly correlated to the presence of charges close to the aromatic rings and with a conformational change of the alkyl chains upon encapsulation.

Full text of DOI:10.1002/chem.200902740

FULL PAPER
DOI: 10.1002/chem.200902740
Induced Chiroptical Changes of a Water-Soluble Cryptophane by
Encapsulation of Guest Molecules and Counterion Effects
Aude Bouchet,[a] Thierry Brotin,*[b] Dominique Cavagnat,[a] and Thierry Buffeteau*[a]
Dedicated to the memory of Andrꢀ Collet
Abstract: We report the synthesis of
the water-soluble cryptophanol deriva-
tive 1 and the study of the chiroptical
properties of its two enantiomers
(>99% ee) by polarimetry, electronic
circular dichroism (ECD), and vibra-
tional circular dichroism (VCD). We
show that cryptophanol 1 exhibits un-
usual chiroptical properties in water
under basic conditions (pH>12). For
instance, the shapes of the ECD and
VCD spectra of 1 in water were strong-
ly dependent on the nature of the
alkali metal ions (Li+, Na+, K+, Cs+)
surrounding the cryptophane and
whether or not a guest molecule is
present inside the cavity of the host. To
the best of our knowledge, this is the
first example in which the nature of
these counterions governs the chiropti-
cal properties of a host molecule.
Moreover, specific ECD spectra were
obtained depending on the size of the
guest molecules. This makes 1 a good
sensor for small neutral molecules in
aqueous solvent. Finally, VCD experi-
ments associated with DFT calculations
show that the chiroptical changes can
be directly correlated to the presence
of charges close to the aromatic rings
and with a conformational change of
the alkyl chains upon encapsulation.
Keywords: chiroptical properties ·
circular dichroism · cryptophane ·
density functional calculations
host–guest systems
·
Introduction
oxy, ethoxy, and propoxy linkers, respectively).[1b] Thus,
ACHTUNGTRENNUNG
cryptophane derivatives can encapsulate a variety of guest
molecules, such as halomethanes and ammonium salts, or
even the xenon atom in organic solution. This gaseous guest
occupies a special place due to its important role in biomed-
ical applications and magnetic resonance imaging.[2] Besides
their interesting binding properties, cryptophane derivatives
are inherently chiral molecules and the presence of six aro-
matic rings interacting together inside a rigid molecular
frame, by an excitonic coupling mechanism, makes the study
of these systems by electronic circular dichroism (ECD)
spectroscopy very attractive.[3] In addition, the enantiopure
derivatives are expected to show a specific ECD response
upon complexation, induced by a conformational change of
the bridges of the cryptophane host. Additional parameters
such as the nature of the solvent, which can compete with
the guest molecule, are also expected to play a key role in
the observed ECD effects.
Cryptophanes are nearly spherical cage molecules composed
of two cyclotriveratrylene (CTV) bowls connected by three
aliphatic linkers. The rigid bowl-shape structure of the cryp-
tophane cavity generates a lipophilic cavity suitable for the
encapsulation of small neutral molecules.[1] The specific mo-
lecular recognition is mainly determined by the internal
volume of the cavity, which in turn is controlled by the
length of the aliphatic linkers (81, 95, and 121 ꢀ3 for meth-
[a] A. Bouchet, Dr. D. Cavagnat, Dr. T. Buffeteau
Institut des Sciences Molꢁculaires (CNRS - UMR5255)
Universitꢁ Bordeaux 1, 351, Cours de la Libꢁration
33405 Talence (France)
Fax : (+33)540008402
E-mail: t.buffeteau@ism.u-bordeaux1.fr
[b] Dr. T. Brotin
Laboratoire de Chimie (CNRS - UMR5182)
Ecole Normale Supꢁrieure de Lyon, 46 Allꢁe dꢂItalie
69364 Lyon (France)
Fax : (+33)472728860
E-mail: t.brotin@ens-lyon.fr
Despite the interesting chiroptical properties of crypto-
phanes, only a very small number of papers have addressed
this topic. This is mainly due to the difficulties for chemists
to synthesize such materials in their enantiopure form in ad-
equate amounts. Collet and co-workers were the first to
report the synthesis of a series of enantio-enriched crypto-
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200902740.
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phanes (90–95% ee) based on the resolution of enantiopure
cyclotriveratrylene units.[3] Unfortunately, the small amount
of material available prevented the complete investigation
of the chiroptical properties of these host molecules as a
function of the nature of the solvent or the presence (or
not) of a guest inside the cavity. In 2003, Brotin and co-
workers reported a novel approach, based on the optical
resolution of cryptophane diastereomers, to provide the two
enantiomers of cryptophane-A and its relatives in fair
amounts.[4] This approach has been used with success to syn-
thesize new enantiopure derivatives, the chiroptical proper-
ties of which have been determined by means of polarimetry
as well as electronic and vibrational circular dichroism spec-
troscopic methods.
insoluble in water. Nevertheless, the synthesis of enantio-
pure water-soluble cryptophanes would be of great interest,
because more pronounced chiroptical effects could be ex-
pected due to the hydrophobic character of the cryptophane
host.
We report in this article the synthesis of the water-soluble
cryptophanol 1 derivative. The chiroptical properties of its
two enantiomers MM-1 and PP-1 in water were investigated
under basic conditions (pH>12) by polarimetry, electronic
circular dichroism, and vibrational circular dichroism. The
effects of the pH, the counterions, and the size of the guest
molecules on the chiroptical properties of host 1 were stud-
ied. Finally, ab initio calculations at the density functional
theory level were performed to interpret the chiroptical
changes.
Vibrational circular dichroism (VCD) can provide more
information than ECD can in the UV/Vis range. The VCD
method measures the differential absorption of left versus
right circularly polarized IR radiation for the 3NÀ6 molecu-
lar vibration transitions, in which N is the number of atoms
in the molecule.[5] Another advantage of VCD is reliable
theoretical support. Quantum mechanical predictions of
VCD spectra are quite successful in replicating the corre-
sponding experimental spectra in the mid IR region.[5c] Ab
initio calculations combined with VCD experiments have
been used during the last two decades to determine the ab-
solute configuration of small and medium-sized mole-
cules[5b–d] and more recently to elucidate supramolecular
structures.[6] Cryptophane molecules are small enough (100–
150 atoms) to allow the use of ab initio calculations at the
density functional theory (DFT) level, allowing the predic-
tion of both the IR and VCD spectra of cryptophanes and
their complexes for given conformations of the bridges.
Thus, for the first time, we have been able to determine the
absolute configuration of the two enantiomers of the crypto-
phane-A derivative and some of its congeners.[7] These stud-
ies also provided information about the conformation of the
linkers. For instance, the presence of bulky guests, such as a
chloroform molecule, inside the cavity of the host molecule
strongly modifies the conformation of the linkers and leads
to a preferential all-trans conformation, whereas the empty
host adopts preferentially a gauche conformation of the
bridges to reduce the volume of its inner cavity.[8] These
VCD experiments as well as the more conventional ECD
and polarimetry experiments have revealed that the solvent
plays a key role in the chiroptical properties of these hosts,
depending on the solventꢂs ability to enter the cavity or not.
However, very small spectral changes were observed in
the IR and VCD spectra of cryptophane-A derivatives when
the size of the guest molecule was changed (42, 56.3, and
72.2 ꢀ3 for xenon, dichloromethane, and chloroform, re-
spectively). Moreover, the poor solubility of cryptophanes
prevents us from investigating the chiroptical properties of
these molecules in a large range of solvents, because a con-
centration of about 10À2 m is usually required for VCD ex-
periments. For instance, these molecules are well soluble in
[D2]dichloromethane and [D]chloroform, sparingly soluble
in 1,1,2,2-[D2]tetrachloroethane, and unfortunately totally
Results
Synthesis of resolved water-soluble cryptophanes: The syn-
thetic route used to obtain water-soluble cryptophanol 1
from cryptophane-A 3 and monofunctionalized cryptopha-
nol 2 derivatives is presented in Scheme 1. Racemic crypto-
Scheme 1. Synthesis of enantiopure cryptophanols MM-1 and PP-1.
phanol 2 was first prepared by a multistep synthesis from
vanillin alcohol according to a procedure described by
Darzac et al.[9] Chiral cryptophanol MM-2 and PP-2 deriva-
tives were prepared from cryptophane diastereomers by re-
action of rac-2 with (À)-camphanic acid chloride according
to a known procedure.[4] The separation of the two dia
ACHTUNGTRENNUNGster-
AHCTUNGTREGeNNUN omers by crystallization in toluene, followed by hydrolysis
under basic conditions, yielded the desired cryptophanols 2
in their enantiopure forms (99–100%). This approach gives
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Chiroptical Changes of a Cryptophane
FULL PAPER
the MM-2 and PP-2 derivatives in fair yield and provides a
sizeable amount (0.1–0.5 g scale) of each enantiomer for
subsequent reactions, taking advantage of the presence of
the reactive hydroxyl group. Thus, the racemic cryptophane-
A rac-3 and its two enantiomers MM-3 and PP-3 were pre-
pared by reaction of rac-2, MM-2, and PP-2, respectively,
with methyl iodide in the presence of cesium carbonate in
N,N-dimethylformamide (DMF) as previously reported.[4]
The following route was used for the synthesis of rac-1
from rac-3 (see Scheme 1): cryptophane-A (0.3 g,
0.34 mmol) was introduced into a 25 mL three-neck flask.
Freshly distilled THF (4 mL) was then added and the sus-
pension was stirred under argon at room temperature. A so-
lution of lithium diphenylphosphide (PPh2Li) in THF
(ꢀ1.0m; 6 mL, 6 mmol) was added dropwise by syringe
under an argon atmosphere (freshly prepared PPh2Li is rec-
ommended for the reaction).[10] After complete addition of
the PPh2Li, the dark red solu-
derivative.[1m] Thus, only two signals with the same intensity
are observed, at 6.6 and 6.7 ppm, respectively, in good
agreement with the D3-symmetrical structure of 1 shown in
Scheme 1. [1: Mp>2508C (decomp); 1H NMR (500 MHz,
[D6]DMSO, 208C): d=8.58 (s, 6H; OH), 6.62 (s, 6H; Ar),
2
6.58 (s, 6H; Ar), 4.40 (d, J
(H,H)=13.4 Hz, 6H; Ha), 4.06
2
(m, 12H; OCH2), 3.17 ppm (d, JACTHUNRTGNEUNG(H,H)=13.4 Hz, 6H; He);
13C NMR (125.6 MHz, [D6]DMSO, 208C): d=146.4 (6C),
144.4 (6C), 134.2 (6C), 130.1 (6C), 120.5 (6C), 117.7 (6C),
68.8 (6C; OCH2), 35.0 ppm (6C; CH2).]
Polarimetric measurements: Polarimetric measurements of
empty MM-1 and MM-1 in the presence of CH2Cl2 and
CHCl3 in water were recorded under basic conditions, ob-
tained by using aqueous solutions of LiOH, NaOH, KOH,
and CsOH at an arbitrary concentration of 0.1m. The optical
rotation values are reported in Table 1 for several wave-
tion was stirred overnight at
Table 1. Optical rotations [a]l25 [10À1 degcm2 gÀ1] of MM-1 and PP-1 at 258C (experimental errors are estimat-
ed to be Æ5%).
608C under argon. Then, the
orange solution was poured
into water; this resulted in a
milky solution forming. The
aqueous phase was extracted
three times with CH2Cl2.
Acidification of the aqueous
phase with concentrated HCl
led to the formation of a white
precipitate, which was collected
589
25
577
25
546
25
436
25
Solvent
Conc [g/100 mL]
[a]
[a]
[a]
[a]
MM-1
PP-1
MM-1
PP-1
MM-1
PP-1
MM-1+CH2Cl2
PP-1+CH2Cl2
MM-1+CHCl3
PP-1+CHCl3
MM-1
MM-1+CH2Cl2
MM-1+CHCl3
MM-1
MM-1+CH2Cl2
MM-1+CHCl3
MM-1
MM-1+CH2Cl2
MM-1+CHCl3
DMF
DMF
DMSO
DMSO
0.16
0.30
0.17
0.20
0.20
0.21
0.19
0.16
0.15
0.19
0.18
0.12
0.23
0.18
0.17
0.19
0.18
0.17
0.25
À173.2
+175.0
À84.3
À183.4
+184.7
À87.8
À212.5
+215.1
À102.0
+97.5
À409.8
+416.1
À192.0
+193.7
+83.2
+87.2
D2O/NaOH
D2O/NaOH
D2O/NaOH
D2O/NaOH
D2O/NaOH
D2O/NaOH
D2O/LiOH
D2O/LiOH
D2O/LiOH
D2O/KOH
D2O/KOH
D2O/KOH
D2O/CsOH
D2O/CsOH
D2O/CsOH
+0.8[a]
+1.8[a]
+2.7[a]
À3.1[a]
À1.4[a]
À26.4
+24.1
À44.4
+42.3
+10.4
À28.4
À33.7
À47.9
À45.3
À47.7
À36.1
À36.1
À35.3
À1.3[a]
À27.6
+25.3
À47.6
+46.8
+10.6
À28.4
À34.0
À51.5
À48.7
À51.9
À38.6
À37.6
À37.3
À1.3[a]
À32.3
+29.0
À53.0
+53.8
+11.2
À30.4
À39.0
À60.6
À59.1
À61.7
À46.7
À45.8
À45.6
+3.8[a]
À47.3
+47.2
À100.0
+103.2
+22.9
on
a
frit and successively
washed with distillated water
and diethyl ether. The solid was
then purified on silica gel (short
column, solvent DMF/acetone
50:50). After evaporation of the
solvent under reduced pressure
and digestion in diethyl ether, a
white-beige precipitate was col-
lected on a frit; this gave 0.2 g
À52.7
À74.0
À153.2
À147.5
À153.1
À120.5
À117.2
À117.9
[a] Optical rotation values with larger experimental errors.
(74%) of
a clean product.
Enantiopure MM-1 (70%) and
PP-1 (74%) derivatives were obtained by using the same
experimental procedure. The nomenclature used to differen-
tiate the two enantiomers of rac-1, rac-2, and rac-3 is that
suggested by Prof. V. Prelog for the specification of the ab-
solute configuration of C3-CTV derivatives in accordance
with IUPAC rules.[11]
lengths and were completed by the values obtained in or-
ganic solvents (DMF, DMSO). As shown in Table 1, polari-
metric measurements were found to be strongly dependent
on the nature of the cations. Indeed, both the sign and the
magnitude of the optical rotation values change drastically
with the nature of the cations. For instance, the optical rota-
tion values of empty MM-1 at the sodium line ([a]589) are
positive and have values of +10.4 and +0.8 for Li+ and
Na+, respectively, whereas [a]589 values are negative and
have values of À47.9 and À36.1 for K+ and Cs+, respective-
ly. Even though the small positive value measured for the
optical rotation in the case of Na+ is questionable, because
its magnitude lies in the range of the experimental error, a
clearly positive value is measured in the case of Li+. This is
the first time that we have observed a reversal of the sign of
the optical rotatory power for a cryptophane host by chang-
The rac-1, MM-1, and PP-1 derivatives were found to be
well soluble in DMSO, DMF, and water under basic condi-
1
tions (pH>12). H NMR spectra of rac-1, MM-1, and PP-1
are reported in the Supporting Information (Figure S1).
These spectra recorded in NaOD or DMSO do not show
any residual methoxy signals in the 3.5–4.0 ppm region. In
addition, the NMR spectra recorded in NaOD solvent do
not show any additional signals in the aromatic region that
could reveal the presence of an “imploded” form of host 1,
as recently observed for another water-soluble cryptophane
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T. Brotin, T. Buffeteau et al.
ing the experimental conditions. As a consequence, the sign
of the optical rotation values cannot be used to determine
the absolute configuration of this water-soluble cryptophane
derivative.
The optical rotation values were also found to be very
sensitive to the presence of a guest molecule in the inner
cavity of 1 for Li+ and Na+ ions. Indeed, a change of the
sign and a significant increase of the optical rotatory power
upon complexation were noticed with respect to the empty
host. On the other hand, no significant changes of the opti-
cal rotation values were observed upon complexation for
K+ and Cs+ ions. Finally, in organic solvents, the optical ro-
tation values were much larger and were found to be strong-
ly dependent on the nature of the solvent.
UV/Vis and ECD measurements: UV/Vis and ECD spectra
of empty MM-1 were recorded at 208C under basic condi-
tions, by using aqueous solutions of LiOH, NaOH, KOH,
and CsOH at an arbitrary concentration of 0.1m. The UV/
Vis spectra (220–360 nm spectral range) of empty MM-1
and MM-1 in the presence of CH2Cl2 and CHCl3 are report-
ed in the Supporting Information (Figure S2). The UV/Vis
spectra exhibit a strong absorption band below 220 nm cor-
1
responding to the allowed Bb transition (Plattꢂs notation) of
the benzene rings and two absorption bands of medium in-
tensity around 240 and 300 nm corresponding to the two
1
1
symmetry forbidden La and Lb transitions of the benzene
rings, respectively. The ECD spectra of empty MM-1 are re-
ported in Figure 1A in the same spectral range and show a
significant change of the Cotton bands of the MM-1 host ac-
cording to the nature of the cation. For instance, similar
ECD spectra are observed for Li+ and Na+, whereas the
ECD spectra of MM-1 undergo a bathochromic shift when
K+ and Cs+ are used. In addition, a significant enhancement
Figure 1. ECD spectra of MM-1: A) in solutions of LiOH, NaOH, KOH,
and CsOH in H2O (0.1m), and B) in NaOH aqueous solution at different
pH values.
1
of the intensity of the Cotton bands associated with the Lb
transition (280–330 nm) occurs for the two latter cations.
Additional experiments were performed with aqueous
NaOH solution at different pH. As shown in Figure 1B, the
ECD spectra are also strongly pH dependent. Indeed, both
1
the Cotton bands associated with the Bb (<230 nm) and the
1Lb (>280 nm) transitions are strongly affected by a change
1
in pH, whereas the Cotton bands of the La transition (240–
260 nm) are less affected. For instance, at a NaOH concen-
tration of 0.0015m, the ECD spectrum contains two Cotton
bands with opposite sign in the 1Lb region and a positive
Cotton band in the 1Bb region. At higher concentration
([NaOH]=1.0m), there are two negative Cotton bands for
1
the Lb transition and a strong negative Cotton band for the
1Bb transition.
Figure 2. ECD spectra of MM-1 in H2O; an aqueous NaOH solution in
the presence of different guests was used. The ECD spectrum of MM-1
in the presence of CCl4 (not shown) is identical to that of the empty
MM-1.
A series of experiments were carried out to investigate
the ability of a guest molecule to enter the cavity of 1. All
the experiments were performed in an aqueous NaOH solu-
tion at an arbitrary concentration of 0.1m. Figure 2 shows
the ECD spectra recorded for the empty or complexed
(methane and chlorinated guests) MM-1 enantiomer. Upon
encapsulation, the ECD spectra reveal a significant change
of the chiroptical properties of 1, which depends on the size
of the guest. The most significant changes occur for the
Cotton bands associated with the 1Bb and 1Lb transitions.
Thus, specific ECD spectra were obtained for CH3Cl@MM-
1, CH2Cl2@MM-1, and CHCl3@MM-1 complexes. However,
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Chiroptical Changes of a Cryptophane
FULL PAPER
when the guest molecule is too small (CH4) or too bulky
(CCl4), the ECD spectrum is identical to that of the empty
host 1. Finally, as expected for two enantiomers, the ECD
spectra of MM-1 and PP-1 show perfect mirror images, with
the presence of an isosbestic point at 239 nm (see Support-
ing Information, Figure S3).
We also investigated the effect of the encapsulation as a
function of the nature of the counterion. Thus, a new series
of experiments were performed with Li+, K+, and Cs+ as
counterions and CH2Cl2 and CHCl3 as guest molecules. The
ECD spectra are reported in Figure 3 for aqueous solutions
havior was seen when Cs+ was used as a counterion (see
Supporting Information, Figure S4). It is remarkable that
the nature of the counterion can have such an influence on
the overall chiroptical properties of the host.
IR and VCD measurements: IR and VCD experiments
were performed on samples in D2O, with a host concentra-
tion of 0.030m to provide VCD spectra with a sufficient
signal-to-noise ratio. IR absorption spectra of rac-1 were re-
corded under various basic conditions using solutions of
NaOD in D2O at different concentrations from 0.056m
(pD=13.6) to 0.592m (pD=14.6). These extremely basic
conditions are essential to dissolve cryptophanol 1 properly
in D2O at a concentration of 0.030m. IR spectra of the
1450–1550 cmÀ1 spectral range, associated with the n19aC=C
stretching vibration of the rings, for which the changes are
the most noteworthy, are reported in Figure 4. There is a
Figure 4. IR spectra of rac-1 in D2O; solutions of NaOD in D2O at differ-
ent concentrations were used. The concentration of host 1 was 0.030m.
clear isobestic point at 1502 cmÀ1 between two main compo-
nents. The respective proportions of the two components
vary considerably according to the concentration of sodium.
At low concentration of NaOD, only the high frequency
component located at 1506 cmÀ1 is observed. When the con-
centration of sodium increases, the low-frequency compo-
nent at 1495 cmÀ1 grows, while the high-frequency compo-
nent collapses. At very high concentration of NaOD
(0.59m), only the low-frequency component is present. It is
worth noting that the molar absorptivity of the low-frequen-
cy component is significantly higher than that of the high-
frequency one. The same behavior occurred when Na+ was
replaced by Li+, K+, and Cs+ ions (see Supporting Informa-
tion, Figures S5 and S6).
Figure 3. ECD spectra of empty MM-1 as well as MM-1 in the presence
of CH2Cl2 and CHCl3 in H2O: aqueous solutions of A) LiOH and B)
KOH were used.
of LiOH and KOH. Interestingly, very surprising host–guest
behavior occurs depending on the counterion used. For in-
stance, similar behavior is observed when Li+ or Na+ is
used as counterion (Figure 3A) and the encapsulation of
CH2Cl2 and CHCl3 results in large changes in the ECD spec-
tra of 1. On the other hand, when K+ is used as a counter-
ion (Figure 3B), the ECD spectra of empty MM-1 and
MM-1 in the presence of CH2Cl2 and CHCl3 remain un-
changed and no encapsulation effect is observed. Similar be-
The IR and VCD spectra of empty and complexed PP-1
are reported in Figure 5. Samples in D2O with 0.21m NaOD
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4511

T. Brotin, T. Buffeteau et al.
of argon or CCl4 in solution does not modify the IR and
VCD spectra of the empty host 1 (spectra not shown). For a
higher concentration in sodium (0.59m), the same spectral
changes occur in the VCD spectra, even for the empty
cryptACTHUNRTGNEUNGophane (see Supporting Information, Figure S7). In this
case, there is no additional spectral change induced by the
presence of the guest molecules. The behavior was similar
when Li+ was used as a counterion (see Supporting Infor-
mation, Figure S8).
A new series of IR and VCD experiments was performed
with solutions of deuterated potassium and cesium hydrox-
ide in D2O at a concentration of 0.21m. As shown in
Figure 6, the absorption (Figure 6A) and VCD (Figure 6B)
Figure 5. A) IR and B) VCD spectra of empty PP-1 as well as Xe@PP-1,
CD2Cl2@PP-1, and CDCl3@PP-1 complexes in D2O; a solution of NaOD
in D2O (0.21m) was used. The concentration of host 1 was 0.030m.
were used. The spectra were recorded in the presence of
various guest molecules (argon, xenon, CD2Cl2, CDCl3, and
CCl4) and are presented in the 1700–1250 cmÀ1 region. The
assignment of cryptophane-A derivatives in this spectral
range has been reported previously.[7a] The bands due to the
n8aC=C and n19aC=C stretching vibrations of the rings occur
at 1595 and 1495 cmÀ1, respectively. The bending vibrations
of CH2 groups give rise to the bands observed in the 1460–
1440 cmÀ1 region. The band located at 1400 cmÀ1 and those
observed between 1350 and 1250 cmÀ1 correspond to cou-
pled modes involving wagging and twisting vibrations of the
CH2 groups (chains and bowls). As shown in Figure 5A,
when a guest molecule is encaged in the host 1, most of the
absorption bands sharpen and are enhanced. This effect, ob-
served when xenon is present in solution, is more pro-
nounced with CD2Cl2 molecules and even more with CDCl3.
This encapsulation effect is also clearly evidenced in the
VCD spectra.
Figure 6. A) IR and B) VCD spectra of empty PP-1 as well as PP-1 in
the presence of xenon, CD2Cl2 and CDCl3 in D2O; a solution of KOD in
D2O (0.21m) was used. The concentration of host 1 was 0.030m.
spectra did not change when any of the guest molecules was
added to the solution. It seems that there is no interaction
between the guest molecules and the cryptophane in KOD
solution. However, it is noteworthy that the VCD spectrum
of empty PP-1 is different in the 1550–1480 cmÀ1 region
from that of the NaOD solution. Indeed, the positive com-
ponent at 1495 cmÀ1 appears in a dispersion profile shape.
As shown in Figure 5B, the bands located at 1495 cmÀ1
and in the 1350–1250 cmÀ1 spectral range are enhanced, and
negative and positive components emerge at 1503 and
1393 cmÀ1, respectively. It is worth noting that the presence
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Chiroptical Changes of a Cryptophane
FULL PAPER
For a higher concentration in potassium (0.59m), as ob-
served previously for the NaOD solution, spectral changes
(i.e., enhancement of the bands located at 1495 cmÀ1 and in
the 1350–1250 cmÀ1 spectral range as well as the emergence
of
a negative and positive components at 1503 and
1393 cmÀ1, respectively) occur both in the presence and in
the absence of a guest molecule in the cavity (see Support-
ing Information, Figure S9). The behavior was similar when
Cs+ was used as counterion (see Supporting Information,
Figure S10).
Discussion
pH effect: The IR experiments performed on rac-1 at differ-
ent concentrations of NaOD (i.e., different pD) reveal the
presence of two components responsible for the absorption
bands associated with the nC=C stretching vibration of the
benzene rings. Thus, for the n19aC=C stretching vibration of
the rings close to 1500 cmÀ1, the two components appear at
1506 and 1495 cmÀ1 and their intensities respond oppositely
as a function of the concentration of sodium (see Figure 4).
The presence of an isosbestic point suggests that there is an
equilibrium between the two different forms of cryptopha-
nol 1. Since the concentration of cryptophanol (i.e., 0.030m)
is not significantly lower than that of the sodium deuterated
hydroxide, we believe that cryptophanol is not totally depro-
tonated and consequently the phenol form of the molecule
coexists with the phenolate form. To confirm this hypothesis,
DFT calculations of the IR spectra were carried out for the
phenol and phenolate forms of the molecule.
Figure 7. Comparison of the experimental IR spectrum of empty PP-1 in
D2O when a solution of NaOD in D2O (0.21m) was used with the calcu-
lated spectra at the B3PW91/6-31G* level for t1t1t1 conformers of the
phenol (6OD) and phenolate (6ONa) forms of PP-1. The half-sum of the
two predicted spectra is also reported (labeled 3OD+3ONa).
correctly analyze the IR and VCD experiments under basic
conditions.
For ECD experiments, it is clear that all the hydroxyl
groups are deprotonated, because the concentration of
cryptACTHNURTGNEUoGN phanol is one thousand times smaller than that of the
The calculated IR spectra at the B3PW91/6-31G* level
for the t1t1t1 conformers of both the phenol (6OD) and phe-
nolate (6ONa) forms of PP-1 are reported in Figure 7 and
are compared with the experimental IR spectrum of empty
PP-1 in D2O with NaOD solution (0.21m). The calculated
IR spectra of the phenol and phenolate forms of PP-1 are
rather different, confirming that the IR spectrum is strongly
affected by the state of ionization of the hydroxyl groups.
Concerning the n19aC=C stretching vibration close to
1500 cmÀ1, the frequency calculated for the phenolate form
is 10 cmÀ1 lower than that calculated for the phenol form,
and its intensity is about twice as high. This result confirms
the spectral changes observed in the IR spectra recorded at
higher concentrations of sodium. It is clear that the low fre-
quency component of the n19aC=C stretching mode is char-
acteristic of the deprotonated phenolate form whereas the
high frequency component is characteristic of the phenol
form of the cryptophanol 1. As shown in Figure 7, the half-
sum of the two calculated spectra (labeled “3OD+3ONa”)
reproduces the experimental spectrum recorded for a 0.21m
sodium concentration fairly well. This result indicates that a
half of the hydroxyl groups are deprotonated when the
sodium concentration is seven times higher than that of the
cryptophanol. On the other hand, for the highest sodium
concentration (i.e., 0.59m), all the hydroxyl groups are de-
protonated. This pH effect must be taken into account to
sodium cations present in solution.
Encapsulation effect: In previous studies, we showed that
VCD and ECD spectra of enantiopure cryptophane A had
very little dependence on the ability of a guest molecule to
enter the cavity of these derivatives or not.[7a,b] Indeed, ex-
periments performed in CD2Cl2, CDCl3, and C2D2Cl4 (a
molecule which cannot enter the cryptophane-A cavity)
reveal no significant differences in the IR and VCD spec-
tra.[7a] Similarly, the ECD spectra recorded of samples in
CHCl3 and CH2Cl2 (two solvents that enter the cavity of
cryptophane-A) and of samples in CH3CN and THF (two
solvents that do not enter the cavity of cryptophane-A)
were quasi-identical, even if small spectral changes were ob-
served in the 260–310 nm region, associated with the 1Lb
transition.[7b] The solvent effect was found more pronounced
for cryptophane-A with C1 symmetry, in particular for crypt-
AHCTUNGTREGoNNUN phane-A monofunctionalized with an electron-withdrawing
triflic moiety or a hydrogen atom.[7b,c] This effect was attrib-
uted to a change of conformation of the linkers upon encap-
sulation.
The ECD and VCD chiroptical changes upon encapsula-
tion are significantly more marked when cryptophanol 1 is
dissolved in water under basic conditions. This was the first
time since we had started studying chiroptical properties of
cryptophanes that such spectral differences in both VCD
Chem. Eur. J. 2010, 16, 4507 – 4518
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4513

T. Brotin, T. Buffeteau et al.
and ECD spectra were observed. It seems reasonable to in-
terpret the chiroptical changes in the following way. Empty
host 1, which is a lipophilic molecule, even though it is solu-
ble under basic conditions (pHꢁ12), adopts a preferential
gauche conformation of the linkers to reduce the size of its
internal cavity in water. In contrast, upon encapsulation, the
presence of a guest molecule inside its cavity requires host 1
to change the conformation of its linkers to enlarge its
cavity and to accommodate a guest molecule. Thus, upon
encapsulation, host 1 adopts preferentially a trans conforma-
tion of the linkers when large molecules are present in the
cavity of 1. This was previously demonstrated for crypto-
phane-A derivatives soluble in organic solvents.[7b,c] Of
course the change of conformation strongly depends on the
size of the guest. A large guest such as a chloroform mole-
cule (van der Waals volume, Vvdw =72.2 ꢀ3)[12] is less easily
accommodated in the cavity of 1 compared to a dichloro-
plex 4.3 kcalmolÀ1 lower in energy than the g1g1g1 conforma-
tion. In addition, no convergence of the optimized geome-
tries of the g1g1g1 conformer was obtained for the phenolate
form. The addition of a chloroform molecule in the crypto-
phanol cage stabilizes the t1t1t1 conformer. A similar result
was previously reported for cryptophane-A monofunctional-
ized with a hydrogen atom.[7c] This result is not surprising,
because there is a better size match between the chloroform
(ca. 72.2 ꢀ3) and the cryptophane cavity in its all-trans con-
formation (ca. 95 ꢀ3).
The VCD spectra calculated at the B3PW91/6-31G* level
for the t1t1t1 and g1g1g1 conformers of the phenol and pheno-
late forms of empty PP-1 are reported in Figure 8A. The
predicted spectra were calculated for each form, taking into
account the Gibbs free energies of the two conformers. Fi-
nally, the half-sum of the two predicted spectra of each form
was calculated for comparison with the experimental VCD
spectrum of empty PP-1 recorded in D2O using a sodium
concentration of 0.21m (see pH effect). Similarly, the half-
ACHTUNGTRENNUNGmethACHTUNGTRENNUNG
ane guest (Vvdw =56.3 ꢀ3) and thus it requires host 1 to
significantly enlarge the size of its cavity.
To confirm that a conformational change of the linkers
can explain the VCD spectral changes, DFT calculations of
the VCD spectra of empty PP-1 and the CDCl3@PP-1 com-
plex were carried out for both the phenol and phenolate
forms of the molecule. For each form, the calculations were
performed for all-gauche (g1g1g1) and all-trans (t1t1t1) confor-
mations of the three linkers. By using starting O-C-C-O di-
hedral angles close to 1808 and À608 for the t1 and g1 con-
formations, respectively, the geometries of the empty and
complexed cavities were optimized at the B3PW91/6-31G*
level. Harmonic vibrational frequencies were calculated at
the same level to confirm that all structures are stable con-
formations and to enable free energies to be calculated. The
converged twist angles between the two CTV bowls, O-C-C-
O dihedral angles, and optimized energies are listed in
Table 2. The optimized geometries of empty PP-1 calculated
for the two conformations lead to very close Gibbs free en-
ergies for both phenol (6OD) and phenolate (6ONa) forms.
Nevertheless, the g1g1g1 conformation is more favorable for
the deprotonated form of the cryptophanol. On the other
hand, for CDCl3@PP-1, the t1t1t1 conformation of the ali-
phatic linkers yields a final optimized structure of the com-
Table 2. Conformations and energies of PP-1.
Optimized
geometries
Energy[a]
Gibbs
DE[b]
Form Conf. D[c] [8] T[d] [8] Electronic
empty PP-1
6OD
t1t1t1
g1g1g1
169.1 37.0
À63.9 41.7
À172.0 73.3
À55.9 46.1
À2755.932758 À2755.212639 0.0
À2755.935483 À2755.212229 0.26
À3726.306559 À3725.628896 0.41
À3726.301043 À3725.629542 0.0
6ONa t1t1t1
g1g1g1
CDCl3@PP-1
6OD
t1t1t1
g1g1g1
168.1 34.7
À69.2 37.6
À165.6 71.1
À4175.032763 À4174.303932 0.0
À4175.028620 À4174.297122 4.3
À5145.388530 À5144.701656 0.0
Figure 8. Comparison of the experimental VCD spectra of A) empty
PP-1 and B) CDCl3@PP-1 complex in D2O when using a solution of
NaOD in D2O (0.21m) with calculated spectra at the B3PW91/6-31G*
level for t1t1t1 and g1g1g1 conformers of the phenol (6OD) and phenolate
(6ONa) forms of PP-1. The half-sum of the two predicted spectra of
6OD and 6ONa is also reported (labeled 3OD+3ONa).
6ONa t1t1t1
g1g1g1 no convergence
[a] In Hartrees. [b] Relative Gibbs energy difference in kcalmolÀ1. [c] Di-
hedral angle O-C-C-O. [d] Twist angle between the 2 CTV units.
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Chiroptical Changes of a Cryptophane
FULL PAPER
sum of the VCD spectra calculated for the t1t1t1 conformer
of the phenol and phenolate form was compared to the ex-
perimental VCD spectrum of CDCl3@PP-1 complex (see
Figure 8B). The spectral changes observed in the experi-
mental spectra upon encapsulation are fairly well repro-
duced in the predicted VCD spectra, showing that a confor-
mational change of the linkers is certainly at the source of
this effect.
The size of the guest molecule plays a key role in the
overall chiroptical properties of water-soluble cryptophanes.
Specific ECD spectra of MM-1 were obtained when chloro-
methane (Vvdw =42 ꢀ3), dichloromethane (Vvdw =56.3 ꢀ3),
and chloroform (Vvdw =72.2 ꢀ3) were used as guest mole-
cules, whereas methane (Vvdw =24 ꢀ3) and tetrachloro
ACHTUNGTNERmNUNG eth-
ACHTUNGTRENNUNG
empty MM-1 (see Figure 2). The tetrachloromethane mole-
cule is too large to be easily accommodated by host 1 and
consequently cannot modify its chiroptical properties. Simi-
lar behavior was observed with the cryptophane-A conge-
ner. In contrast, methane easily enters the cavity of 1, but its
volume is too small to interact strongly with 1, thus leaving
the conformation of the bridges unchanged.
Other guest molecules such as CH2BrCl (Vvdw =60.4 ꢀ3),
CH2Br2 (Vvdw =64.4 ꢀ3), and CH3I (Vvdw =54.6 ꢀ3) are also
well recognized by MM-1 and the ECD spectra of these
complexes differ from each other (see Figure 9A). Thus,
host 1 selectively recognizes each encapsulated species, even
if there is a small difference in size between these three
guests. In contrast, the ECD spectrum of MM-1 with CH2I2
(Vvdw =76.5 ꢀ3) is perfectly identical (at least in the 1Lb spec-
tral region) to that of the empty host, suggesting that this
guest is too large to enter the cavity of 1. The ability of the
ECD spectroscopy to discriminate supramolecular com-
plexes of 1 with small neutral molecules is a remarkable
characteristic of this host and it could find applications for
the detection of chlorinated solvents dissolved in water. This
encapsulation effect is essentially governed by the size of
the guest molecules in water, but seems not dependent on
the nature of the guest. Indeed, as shown in Figure 9B, simi-
lar ECD spectra were recorded when chloromethane or
xenon were introduced into the solution. These two gases
are interesting guest molecules because they have the same
volume (Vvdw =42 ꢀ3), but different chemical properties.
It is worth noting that a change in the pH conditions pro-
duces similar effects on the ECD spectra (see Figure 1B) as
that produced by the presence of a guest molecule inside
the cavity of 1. Thus, an increase of the concentration of cat-
ions certainly favors a preferential trans conformation of the
linkers. Finally, the high selectivity of water-soluble crypto-
phane for guest molecules is related to the presence of the
phenolate form of the two CTV units, which enhances the
chiroptical properties of host 1 (the deviation of the elec-
Figure 9. ECD spectra of MM-1 in H2O when using an aqueous NaOH
solution in the presence of different guests.
phanes. Two distinct effects were observed upon encapsula-
tion depending on the size of the counterions. For Li+ (V=
1.8 ꢀ3) and Na+ (V=4.4 ꢀ3) cations,[13] the encapsulation of
CH2Cl2 and CHCl3 results in large changes in the ECD and
VCD spectra of 1, whereas for K+ (V=11.0 ꢀ3) and Cs+
(V=19.5 ꢀ3) no encapsulation effect was observed: the
ECD and VCD spectra as well as the optical rotation values
remained unchanged compared to the empty cryptophanol
1. Many allosteric effects upon encapsulation have been re-
ported in the literature,[14] but to our knowledge this is the
first time that changing the nature of the alkali metal cation
induces such large changes in both the ECD and VCD spec-
tra of a host molecule. In our opinion, this surprising behav-
ior can be more easily interpreted by steric effects than by
electronic effects. Indeed, host 1 and its congeners are inher-
ently chiral molecules composed of two cyclotriveratrylene
units connected by three ethylenedioxy bridges. This struc-
ture generates a lipophilic cavity (Vꢀ95 ꢀ3) suitable for the
encapsulation of small guest molecules. Before entering the
cavity, the guest molecule must cross one of the three por-
tals to access the inner cavity of 1. Under basic conditions,
the size of the counterions surrounding the host molecule
may prevent the guest molecule from reaching the cavity.
1
1
tronic transition moment Lb and Bb induced by the pheno-
late moiety is larger than that induced by the phenol group).
Counterion effect: The counterion also plays a key role in
the overall chiroptical properties of water-soluble crypto-
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4515

T. Brotin, T. Buffeteau et al.
Our results demonstrate that the potassium and cesium cat-
ions are large enough to prevent CH2Cl2 and CHCl3 from
entering the cavity of 1. In contrast, the size of the lithium
and sodium cations, significantly smaller, is not sufficient to
obstruct the portals and allows guest molecules to enter the
cavity of 1. This assumption can be supported by examina-
tion of the optimized structures of PP-1 for the phenolate
form when using sodium and cesium cations. As shown in
Figure 10, even if the six sodium cations are placed in front
of the portals of 1, they allow the entrance of CDCl3 mole-
cules. On the other hand, for bulky cations (cesium), the
access to the cavity is impossible and no encapsulation
effect can be observed. Counterions appear as an external
factor, which can modify the chiroptical properties of the
host by controlling the access of the guest to the inner
cavity of 1.
signal is detected under similar conditions, reflecting the ab-
sence of complex formation. UV/Vis spectroscopy of rac-1
performed under different conditions (see Supporting Infor-
mation, Figure S2) is also consistent with the overall ECD
and VCD experiments. For instance, for LiOH and NaOH
solutions, both CH2Cl2@rac-1 and CHCl3@rac-1 show slight-
ly different UV/Vis spectra compared to that of the empty
rac-1, as a consequence of the encapsulation process. In con-
trast, for KOH and CsOH solutions, UV/Vis spectra are
strictly identical, which is consistent with the absence of en-
capsulation under these conditions.
Conclusion
The two enantiomers of cryptophanol 1 were synthesized,
and their chiroptical properties in water under basic condi-
tions (pH>12) were examined by polarimetry as well as
ECD and VCD spectroscopy. The ECD and VCD experi-
ments were performed by varying some parameters such as
the nature of the counterion, the size of the guest molecule,
and the pH conditions. Our results reveal unique behavior
of host 1, never observed with cryptophane-A and its rela-
tives in organic solvents before. We showed that both the
ECD and VCD spectra of 1 are extremely sensitive to exter-
nal parameters such as the nature of the counterion (alkali
metal Li+, Na+, K+, and Cs+) and the pH of the solution.
Polarimetric measurements also reveal a change of the sign
of the optical rotation values with respect to the used coun-
terions. As a consequence, the determination of the absolute
configuration of water-soluble cryptophanes should be ex-
amined with great caution, and the use of several chiroptical
techniques (ECD, VCD) are thus recommended to ascertain
the absolute configurations of these molecules. The aqueous
solvent used under basic conditions seems to play a key role
in the observed effect. Indeed, the antagonism between
cryptophane (lipophilic molecule) and water induces a con-
traction of the host, which preferentially adopts a gauche
conformation of the linkers to reduce the size of its internal
cavity. Moreover, the presence of six phenolate moieties
under basic conditions amplifies the chiroptical properties
(ECD) of 1, because they induce a larger deviation of the
Figure 10. B3PW91/6-31G*-optimized structures of PP-1 for the pheno-
late form when using sodium (left) and cesium (right) cations.
Similar behavior occurs in methanol, which shows no en-
capsulation effect on the ECD spectra of MM-1 in the pres-
ence of CH2Cl2 or CHCl3 (see Supporting Information, Fig-
ure S11). Steric congestion of the host surrounded by metha-
nol molecules can also explain this feature. Indeed, metha-
nol molecules can strongly interact with phenol groups by
hydrogen-bonding interactions. Since the methanol mole-
cules are unable to enter the cavity of cryptophane mole-
cules, they stay at the periphery, close to the three portals of
the host. Thus, methanol molecules (Vvdw =36.1 ꢀ3)[12] play a
role similar to that of potassium and cesium cations by pre-
venting guest molecules from reaching the inner cavity of 1.
1H NMR and UV/visible spectroscopy performed on rac-1
1
1
1
angle for both the Bb, La, and Lb transition moments com-
pared to the protonated species (experiments in methanol).
The ECD and VCD experiments have shown the impor-
tance of the nature of the cation on the overall chiroptical
properties of 1. This surprising counterion effect can be
more easily interpreted on the basis of steric effects. Small
cations such as Li+ or Na+ are not bulky enough to obstruct
the three portals of the host 1 and thus allow the guest mol-
ecules to enter the cavity of 1. In turn, these guest molecules
induce a conformational change, allowing the cryptophane
to adopt an all-trans conformation of the linkers. As the size
of the guest increases, the host 1 adopts a conformation of
the linkers that enhances the size of its internal cavity (trans
conformation) to accommodate the guest more easily. In
contrast, the empty cryptophane in aqueous solution tends
1
nicely confirm these results. For instance, the H NMR spec-
tra (see Supporting Information, Figure S12) of empty rac-1,
CH2Cl2@rac-1, and CHCl3@rac-1 show a clear difference in
the NMR signals for the bridges (d=4.7–3.8 ppm region);
this supports the concept of a change of conformation of the
linkers upon encapsulation, which also depends on the
nature of the guest molecule. In addition, for the
CH2Cl2@rac-1 complex in NaOD solution, a bound signal is
clearly visible around 1.0 ppm, which is characteristic of a
high-field-shifted signal due to the shielding effect of the six
aromatic rings. In contrast, in KOD solution, no bound
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Chiroptical Changes of a Cryptophane
FULL PAPER
À
À
OCH2CH2O bridges were considered either with an anti conformation
(referring to the bonds to the O atoms having a 1808 dihedral angle, la-
beled t1t1t1) or with a gauche conformation (À608 dihedral angle, labeled
g1g1g1). In a second step, geometry optimizations were performed by in-
troducing a chloroform molecule inside the cryptophanol cavity, consider-
ing either a t1 or g1 conformation for the three ethoxy linkers (t1t1t1 and
g1g1g1 conformers). Vibrational frequencies, IR, and VCD intensities
were calculated at the same level of theory, utilizing the magnetic field
perturbation method with gauge-invariant atomic orbitals.[18] For compar-
ison to experiment, the calculated frequencies were scaled by 0.968 and
the calculated intensities were converted into Lorentzian bands with a
to reduce its internal volume and preferentially adopts a
gauche conformation of the linkers. Different behavior
occurs for the K+ and Cs+ ions. Indeed, these two cations
seem large enough to obstruct the portals of 1 and to pre-
vent any guest from entering the cavity of the host. As a
consequence, the chiroptical properties of the host remain
unchanged. To our knowledge, this is the first time that such
a counterion effect has been reported for a chiral host mole-
cule. In addition, chiroptical properties of MM-1 (in particu-
lar the ECD spectra) are strongly affected by the encapsula-
tion of a guest molecule present inside the cavity, giving spe-
cific ECD spectra for various sizes of the guest molecules.
This makes 1 a good sensor for the detection of small neu-
tral molecules dissolved in water, and such a system could
find application in environmental science.
half-width of 7 cmÀ1
.
Acknowledgements
The authors are indebted to the CNRS (Chemistry Department) and to
Rꢁgion Aquitaine for financial support for FTIR and optical equipment.
They also acknowledge computational facilities provided by the Pꢆle
Modꢁlisation of the Institut des Sciences Molꢁculaires and the M3PEC-
Mꢁsocentre of the University Bordeaux
u-bordeaux1.fr), financed by the Conseil Rꢁgional dꢂAquitaine and the
French Ministry of Research and Technology.
1
(http://www.m3pec.
Experimental Section
Polarimetric measurements: Optical rotations of MM-1 and PP-1 were
measured at several wavelengths on a Jasco P-1010 polarimeter with a
100 mm cell thermostated at 258C.
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UV/Vis and ECD measurements: UV/Vis and ECD spectra were record-
ed on Jasco V-550 and Chirascan spectrophotometers, respectively, at
room temperature, and by using
a 0.2 cm path length quartz cell
(Hellma). The concentration of cryptophanol 1 was in the range of 5ꢄ
10À5 to 10À4 m in basic H2O solutions (0.1m solutions of LiOH, NaOH,
KOH, and CsOH). Spectra were recorded in the 220–450 nm wavelength
range with a 0.5 nm increment and a 1 s integration time. Spectra were
processed with Chirascan software, baseline-corrected, and slightly
smoothed by using a third-order least-square polynomial fit. Spectral
units were expressed in molar ellipticity.
IR and VCD measurements: The IR and VCD spectra were recorded on
a ThermoNicolet Nexus 670 FTIR spectrometer equipped with a VCD
optical bench.[15] IR absorption and VCD spectra were recorded at a res-
olution of 4 cmÀ1, by co-adding 50 scans and 24000 scans (8 h acquisition
time), respectively. Samples were contained in a CaF2 cell with a fixed
path length of 45 mm (BioCellꢅ, BioTools). IR and VCD spectra were
obtained of MM-1 and PP-1 in basic D2O solutions (0.21m and 0.59m sol-
utions of LiOD, NaOD, KOD, and CsOD) at a concentration of 0.030m.
Additional IR spectra of rac-1 were recorded for various concentrations
of LiOD, NaOD, KOD, and CsOD. Baseline corrections of the VCD
spectra were performed by subtracting the two opposite-enantiomer
VCD spectra of 1 (recorded under the same experimental conditions)
with division by two. In all experiments, the photoelastic modulator was
adjusted for a maximum efficiency at 1400 cmÀ1. Calculations were car-
ried out with the standard ThermoNicolet software, using Happ and
Genzel apodization, de-Haseth phase-correction, and a zero-filling factor
of one. Calibration spectra were recorded using a birefringent plate
(CdSe) and a second BaF2 wire grid polarizer, following the experimental
procedure previously published.[16] Finally, in the presented IR spectra,
the solvent absorption was subtracted out.
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Received: October 5, 2009
Published online: March 16, 2010
4518
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