Chiroptical sensing of asymmetric hydrocarbons using a homochiral supramolecular box from a bismetalloporphyrin rotamer

Article abstract of DOI:10.1002/anie.200604330

(Chemical Equation Presented) The surrounding shapes the box: The zinc porphyrin dimer 1 bearing pyridyl groups can chiroptically sense an asymmetric hydrocarbon, such as limonene, by forming the homochiral box-shaped tetrameric assembly BOX_⊥.

Full text of DOI:10.1002/anie.200604330

Angewandte
Chemie
DOI: 10.1002/anie.200604330
Molecular Recognition
Chiroptical Sensing of Asymmetric Hydrocarbons Using a Homochiral
Supramolecular Box from a Bismetalloporphyrin Rotamer
Junko Aimi, Kazumasa Oya, Akihiko Tsuda,* and Takuzo Aida*
Molecular recognition of hydrocarbons is one of the chal-
lenging subjects in supramolecular chemistry.[1,2] Here we
describe the chiroptical sensing of asymmetric hydrocarbons
with an achiral organic dye molecule that self-assembles to
form a box-shaped chiral cyclic tetramer.[3,4] Chiroptical
sensing of asymmetric molecules is a method in which a
chromophoric host is allowed to interact with a chiral
guest.[5–11] When the chiral guest is appropriately associated
with the host molecule through multipoint interactions,[12] the
host displays a circular dichroism (CD) response in the visible
absorption region, which can be diagnosed without interfer-
ence from other coexisting molecules. Here, the sign and
intensity of the CD response reflects the absolute config-
uration and enantiomeric purity, respectively, of the chiral
guest.[13] For chiroptical sensing of asymmetric hydrocarbons,
only limited examples have so far been reported,[2] since these
compounds do not possess appropriate functionalities for
directional multipoint interactions.[1]
Our strategy for chiroptical sensing makes use of a box-
shaped chiral supramolecular assembly of the bismetallopor-
phyrin rotamer 1.[3,14,15] In the presence of an asymmetric
hydrocarbon, such as limonene, enrichment of either of the
two enantiomeric forms of the chiral box takes place, thereby
allowing an enhanced CD response in the visible absorption
region. This is based on our recent finding that the zinc
complex of dialkynylene-linked bisporphyrin 2 with meso
pyridyl groups self-assembles to form a box-shaped cyclic
tetramer (BOX), where 2 as the building block adopts either a
planar (k ) or
a
perpendicular (? ) conformation
(Scheme 1).[3] While BOXk consisting of the planar conformer
of 2 (2k) is achiral, BOX? composed of its perpendicular
conformer (2?) is chiral (homochiral). Since only the latter
assembly is eligible for chiroptical sensing, we synthesized 1, a
new tetraalkynylene version of 2, with an expectation that the
[*] J. Aimi, K. Oya, Dr. A. Tsuda, Prof. Dr. T. Aida
Department of Chemistry and Biotechnology
School of Engineering
The University of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)
Fax : (+81)3-5841-7310
E-mail: tsuda@macro.t.u-tokyo.ac.jp
aida@macro.t.u-tokyo.ac.jp
Homepage: http://macro.chem.t.u-tokyo.ac.jp/
J. Aimi, Dr. A. Tsuda
PRESTO
Japan Science Technology Agency (JST)
4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan)
Scheme 1. Schematic representations of rotamer 1 and its self-assem-
bling event. Pink cylinders represent spacers consisting of oligoalkynyl-
ene units, while red arrows indicate the direction of Py!Zn coordina-
tion.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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energetic demand for the planarization of 1, leading to achiral
BOXk, must be lower than that for 2.
The tetraalkynylene-linked zinc porphyrin dimer 1 was
synthesized by a procedure similar to that reported for 2.[3b]
The 1H NMR spectrum and the absorption and emission
spectral features of 1, along with its size-exclusion chromato-
graphic profile (SEC),[16] indicate that 1 self-assembles to
form a box-shaped cyclic tetramer in a manner analogous to
the self-assembly of 2.[3,17] In CDCl3 at 208C, compound 1
shows two Soret absorption bands at 458 and 485 nm,
assignable to BOX? and BOXk, respectively, where the
1
molar ratio BOX?/BOXk, as determined by H NMR spec-
troscopy, is nearly unity.[18] To our surprise, the supramolec-
ular assemblies of 1 are rather resistant to dissociation, and
the enantiomers of BOX? were successfully separated from
one another by means of chiral HPLC on a SUMICHIRAL
OA-3100 column using CH2Cl2/hexane (3:7) as the
eluent.[17b,19] When the chiral HPLC profile of self-assembled
1 was traced at 208C by the absorbance change at 455 nm
mostly due to BOX?, two elution peaks appeared at 6.1 and
8.5 min (Figure 1a). By monitoring the CD intensity change
at 455 nm, the former and latter elution peaks were found to
exhibit responses of positive and negative sign, respectively.
On the other hand, an HPLC trace recorded by monitoring
the absorbance change at 485 nm due to BOXk displayed only
a single elution peak (Figure 1b). Apparently the two elution
peaks in Figure 1a can be assigned to the enantiomers of
Figure 1. Chiral HPLC profiles of self-assembled 1 using CH2Cl2/
hexane (3:7) as an eluent at 208C, monitored by absorption (and CD)
responses at a) 455 and b) 485 nm.
homochiral BOX? consisting of the perpendicular conformer
of 1 (1?), while the single elution peak in Figure 1b is due to
achiral BOXk composed of the planar conformer of 1 (1k). In
fact, the two fractions of BOX? in Figure 1a, after chromato-
graphic isolation, displayed mirror-image CD spectra (Fig-
ure 2c and e), whereby a very large CD spectral intensity of
the first fraction is noteworthy. By reference to Figure 2b, the
Figure 2. CD and absorption spectra of self-assembled 1 in CH2Cl2/hexane (3:7) at 208C before (a,b) and after chiral HPLC with CH2Cl2/hexane
(3:7) as an eluent (first (c,d) and second (e,f) fractions). Blue and red dots mark the Q-bands of BOX? and BOXk, respectively.
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absorption spectrum of the first fraction predominantly
contains only one set of the zinc porphyrin Soret and Q-
bands assignable to BOX? (Figure 2d),[3] while that of the
second fraction appears to include, besides the above set,
another set of these absorption bands, assignable to BOXk
(Figure 2 f). Considering also the fact that the CD spectral
intensity of the second fraction (Figure 2e) is much lower
than that of the first fraction (Figure 2c), the second fraction
is apparently contaminated with achiral BOXk as well as the
enantiomeric counterpart of homochiral BOX?. Judging from
the intense CD spectrum of the first fraction, homochiral
BOX? can be characterized by a very large molar molecular
ellipticity. In fact, at the absorption maximum of the Soret
band (458 nm), j De j of BOX? is estimated to be at least
3640 cmꢀ1mꢀ1 (910 cmꢀ1mꢀ1 per unit of 1?).[20]
chiroptical activity as a result of the accelerated dissociation
and reassembly of the building block.
The dynamic self-assembling behavior of 1 to form
homochiral BOX?, thus observed, prompted us to explore
its potential for the chiroptical sensing of asymmetric hydro-
carbons. For this purpose we chose limonene, since both
enantiomers are available. Electronic absorption spectrosco-
py of a (R)-limonene solution of 1 (3.0 mL; [1] = 6.24 ”
10ꢀ6 mm), which was allowed to stand for 1 day at 208C,
showed a Soret absorption band at 458.5 nm characteristic of
BOX? with a red-shifted shoulder at 487.5 nm due to BOXk.
While (R)-limonene is chiroptically silent in the visible
absorption region, the (R)-limonene solution of 1 displayed
clear CD bands at 440–480 nm (Figure 4a, solid curve) with
split Cotton effects [lmax = 468 (q = + 2.0), 460 (ꢀ5.5), and
451 nm (+ 2.3mdeg)]. Use of ( S)-limonene as the solvent
resulted in a mirror-image CD spectrum (broken curve) of
BOX? observed in (R)-limonene. These CD spectral features
are essentially identical to those of the chromatographically
isolated enantiomers of BOX? (Figure 2), indicating that
either of the two enantiomers of BOX? is thermodynamically
enriched in limonene depending on its absolute configuration.
We found that the chiroptical activity of BOX? at ambient
temperatures lasts for a rather long period of time. For
example, in CH2Cl2/hexane (3:7) at 20 8C, the CD intensity of
BOX? (first fraction in chiral HPLC) decreased only slowly
with a half-life (t1/2) of 11.5 h (Figure 3a), where the pseudo-
first-order rate constant, as estimated from the initial slope of
the racemization, was 1.67 ” 10ꢀ5 sꢀ1 (r2 = 0.999). On the other
hand, when the sample was heated to 508C, t1/2 was consid-
erably shortened to 15 min. Arrhenius plots of the kinetic
data obtained at 10–508C provided an activation energy for
the racemization of 97.5 kJmolꢀ1 (Figure 3b). Such a large
thermodynamic stability of BOX? most likely arises from the
ꢀ
eight Zn N coordination bonds involved. Nevertheless,
addition of a coordinating base, such as pyridine, to the
sample solution resulted in rapid disappearance of its
Figure 4. a) CD spectra of 1 (6.2”10ꢀ6 m) at 208C in (R)- and (S)-
limonene (solid and broken line, respectively). b) CD intensity at
460 nm of 1 as a function of the enantiomeric excess (%) of limonene.
c) Plots of CD intensity at 460 nm after 100-fold dilution of a (S)-
limonene solution of 1 (0.03 mL, [1]=6.2”10ꢀ4 m) with 3.0 mL of (R)-
limonene.
Figure 3. a) Time-dependent changes in CD intensity at 460 nm of
BOX? from 1, obtained as the first fraction in chiral HPLC, at 10–508C
in CH2Cl2/hexane (3:7). b) Arrhenius plot of the pseudo-first-order rate
constants of racemization obtained from (a).
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Communications
for 15 min at room temperature. Then, the reaction mixture was
extracted with CHCl3/H2O, and the combined organic extracts were
dried over anhydrous Na2SO4 and concentrated to dryness. A CHCl3
solution of this residue was treated with 6n aq. HCl to allow
demetalation, washed with aq. NaHCO3 and water, dried over
anhydrous Na2SO4, and then concentrated to dryness. The residue
was subjected to size exclusion chromatography (SEC) with toluene
as an eluent; the first fraction was collected and stirred in CHCl3 with
an excess amount of Zn(OAc)2 for 1 h. Then, the reaction mixture
was extracted with CHCl3/H2O, and the combined organic extracts
were dried over anhydrous Na2SO4 and concentrated to dryness.
Recrystallization of the residue from CHCl3/MeCN gave 1 as green
solid in 85% yield (42 mg, 24 mmol). Free-base form of 1: MALDI-
TOF MS: m/z: 1758, [M+H]+ calcd for C118H136N10O4: 1759; UV/Vis
As shown in Figure 4b, when 1 was dissolved in limonene
at varying molar ratios of its enantiomers, the observed CD
intensity of the resulting solution at, for example, 460 nm
changed in linear proportion to the enantiomeric excess of
limonene. Thus, the enantiomeric purity of limonene can be
readily determined. In relation to this result, upon 100-fold
dilution of a (S)-limonene solution of 1 (30 mL, [1] = 6.2 ”
10ꢀ4 m) with (R)-limonene, an inversion of the CD sign of
BOX? certainly took place but only very slowly at 208C to
reach a plateau in 24 h (Figure 4c). Thus, the chiroptical
memory[5,9,21] of BOX? is long-lived, as expected from the
large activation energy for racemization (vide ante). How-
ever, as beneficial for quick chiroptical sensing, a trace
amount of THF, a weakly coordinating base, considerably
shortened the time for thermodynamic equilibrium to be
reached, without affecting the CD intensity finally attained.
By reference to the CD intensity at 458 nm of BOX?,
separated as the first fraction in chiral HPLC (Figure 2d), the
enantiomeric excess of BOX? in limonene was estimated to
be at most 3%. Therefore, the successful chiroptical sensing
of limonene takes great advantage of the inherently large
molecular ellipticity of enantiomerically pure BOX?. A CPK
model study predicted that BOX? is likely to adopt a
rectangular shape, whose inner space (1 ” 1 ” 2 nm) can
accommodate four to six molecules of limonene. The extra-
ordinary large molecular ellipticity of BOX? implies that it
might be distorted in an orthorhombic manner for minimi-
zation of the vacancy in the solvent-included inner space.
In conclusion, we have demonstrated that the zinc
complex of a bisporphyrin bearing pyridyl groups, 1, can
chiroptically sense an asymmetric hydrocarbon, such as
limonene, by forming a homochiral box-shaped tetrameric
assembly, BOX?. Chiroptical sensing can be performed
readily by addition of 1 to limonene; because the BOX?
formed is enantiomerically enriched, the optical purity and
the absolute configuration of limonene can be determined.
While the extent of the enantiomeric enrichment is small, the
extremely large molecular ellipticity of chiral BOX? enables
sensitive chiroptical visualization.
1
(CHCl3): lmax = 466, 493, 624, 675 nm; H NMR (500 MHz, CDCl3):
d = ꢀ2.61 (s, NH), 0.83(t, J = 6.8 Hz, Me), 1.23–1.38 (br, alkyl), 1.52
(t, J = 7.5 Hz, alkyl), 1.89 (t, J = 7.5 Hz, alkyl), 4.15 (t, J = 6.5 Hz,
alkyl), 6.93(s, Ar), 7.36 (d, J = 2.2 Hz, Ar), 8.12 (d, J = 5.7 Hz, Py),
8.80 (d, J = 5.0 Hz, pyrrole-b), 8.86 (d, J = 5.0 Hz, pyrrole-b), 9.02 (d,
J = 5.0 Hz, pyrrole-b), 9.06 (d, J = 5.7 Hz, Py), 9.09 (d, J = 5.0 Hz,
pyrrole-b), 9.18 (d, J = 5.0 Hz, pyrrole-b), 9.20 (d, J = 5.0 Hz, pyrrole-
b), 9.62 (d, J = 5.0 Hz, pyrrole-b), 9.64 (d, J = 5.0 Hz, pyrrole-b), and
10.08 ppm (s, meso). 1: MALDI-TOF MS: m/z: 1885, [M+H]+ calcd
for C118H132N10O4Zn2: 1885; UV/Vis (CHCl3): lmax (e mꢀ1 cmꢀ1) = 458
(154000), 485 (47100), 638 (30000), 666 (29400) nm; 1H NMR
(500 MHz, CDCl3, 208C, BOX?/BOXk = 1:1): d = 0.73–1.88 (br,
alkyl), 2.14 (d, J = 10.5 Hz, Py), 2.75 (d, J = 10.5 Hz, Py), 4.02–4.10
(m, alkyl), 6.17 (d, J = 10.5 Hz, Py), 6.38 (d, J = 10.5 Hz, Py), 6.84 (s,
Ar), 7.30 (s, Ar), 7.38 (s, Ar), 7.47 (d, J = 5.0 Hz, pyrrole-b), 7.73(d,
J = 5.0 Hz, pyrrole-b), 8.93(d, J = 5.0 Hz, pyrrole-b), 8.94 (d, J =
5.0 Hz, pyrrole-b), 9.07 (d, J = 5.0 Hz, pyrrole-b), 9.14 (d, J = 5.0 Hz,
pyrrole-b), 9.17 (d, J = 5.0 Hz, pyrrole-b), 9.27 (d, J = 5.0 Hz, pyrrole-
b), 9.28 (d, J = 5.0 Hz, pyrrole-b), 9.45 (d, J = 5.0 Hz, pyrrole-b,
BOXk), 9.47 (d, J = 5.0 Hz, pyrrole-b, BOX?), 9.75 (d, J = 5.0 Hz,
pyrrole-b), 9.76 (d, J = 5.0 Hz, pyrrole-b), 10.05 (s, meso, BOX?) and
10.06 ppm (s, meso, BOXk).
Received: October 23, 2006
Published online: February 9, 2007
Keywords: chiroptical sensing · hydrocarbons ·
.
molecular recognition · porphyrinoids · self-assembly
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Experimental Section
Most reagents and solvents were used as received from commercial
sources without further purification. (R)-Limonene (97% ee) and (S)-
limonene (96% ee) were purchased from Aldrich. For column
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57 mmol) and CuCl (440 mg, 4.48 mmol), and the mixture was stirred
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