Supramolecular Photochirogenesis Driven by Higher-Order Complexation: Enantiodifferentiating Photocyclodimerization of 2-Anthracenecarboxylate to Slipped Cyclodimers via a 2:2 Complex with β-Cyclodextrin

Article abstract of DOI:10.1021/jacs.7b12085

Chiral slipped 5,8:9′,10′-cyclodimers were preferentially produced over classical 9,10:9′,10′-cyclodimers upon supramolecular photocyclodimerization of 2-anthracenecarboxylate (AC) mediated by β-cyclodextrin (β-CD). This photochirogenic route to the slipped cyclodimers, exclusively head-to-tail (HT) and highly enantioselective, has long been overlooked in foregoing studies but is dominant in reality and is absolutely supramolecularly activated by 2:2 complexation of AC with β-CD. The intricate structural and photophysical aspects of this higher-order complexation-triggered process have been comprehensively elucidated, while the absolute configurations of the slipped cyclodimers have been unambiguously assigned by comparing the experimental and theoretical circular dichroism spectra. In the 2:2 complex, two ACs packed in a dual β-CD capsule are not fully overlapped with each other but are only partially stacked in a slipped anti- or syn-HT manner. Hence, they do not spontaneously cyclodimerize upon photoexcitation but instead emit long-lived excimer fluorescence at wavelengths slightly longer than the monomer fluorescence, indicating that the slipped excimer is neither extremely reactive nor completely relaxed in conformation and energy. Because of the slipped conformation of the AC pair in the soft capsule, the subsequent photocyclodimerization becomes manipulable by various internal or external factors, such as temperature, pressure, added salt, and host modification, enabling us to exclusively obtain the slipped cyclodimers with high regio- and enantioselectivities. In this supramolecularly driven photochirogenesis, the dual β-CD capsule functions as a chiral organophotocatalyst to trigger and accelerate the nonclassical photochirogenic route to slipped cyclodimers by preorganizing the conformation of the encapsulated AC pair, formally mimicking a catalytic antibody.

Full text of DOI:10.1021/jacs.7b12085

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Article
Supramolecular Photochirogenesis Driven by Higher-Order Complexation.
Enantiodifferentiating Photocyclodimerization of 2-Anthracenecarboxylate
to Slipped Cyclodimers via 2:2 Complex with #-Cyclodextrin
Xueqin Wei, Wanhua Wu, Ryohei Matsushita, Zhiqiang Yan, Dayang Zhou, Jason J.
Chruma, Masaki Nishijima, Gaku Fukuhara, Tadashi Mori, Yoshihisa Inoue, and Cheng Yang
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b12085 • Publication Date (Web): 13 Feb 2018
Downloaded from http://pubs.acs.org on February 13, 2018
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Supramolecular Photochirogenesis Driven by Higher-Order Complexation.
Enantiodifferentiating Photocyclodimerization of 2-Anthracenecarboxylate to
Slipped Cyclodimers via 2:2 Complex with
β
-Cyclodextrin
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†
,#
†,#
‡,#
†,#
§
Xueqin Wei, Wanhua Wu, Ryohei Matsushita, Zhiqiang Yan, Dayang Zhou, Jason J.
†
, ⊥
¶
||
‡
,‡
Chruma, Masaki Nishijima, Gaku Fukuhara, Tadashi Mori, Yoshihisa Inoue,* and Cheng
,
†
Yang*
†
Key Laboratory of Green Chemistry & Technology, College of Chemistry, State Key
Laboratory of Biotherapy, West China Medical Center, Healthy Food Evaluation Research
⊥
Center, and Sino-British Materials Research Institute, College of Physical Sciences and
Technology, Sichuan University, 29 Wangjiang Road, Chengdu, 610064, China
‡
¶
Department of Applied Chemistry and Office for University-Industry Co-creation, Osaka
University, Yamada-oka, Suita565-0871, Japan
§
Comprehensive Analysis Center, ISIR, Osaka University, Mihogaoka, Ibaraki 567-0047, Japan
Department of Chemistry, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo
||
152-8551, Japan
Emails: inoue@chem.eng.osaka-u.ac.jp; yangchengyc@scu.edu.cn
#
Equal contributions.
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ABSTRACT: Chiral slipped 5,8:9',10'ꢀcyclodimers were preferentially produced over classical
9
,10:9',10'ꢀcyclodimers upon supramolecular photocyclodimerization of 2ꢀanthracenecarboxylate
(AC) mediated by ꢀcyclodextrin ( ꢀCD). This photochirogenic route to the slipped cyclodimers,
β
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exclusively head-to-tail (HT) and highly enantioselective, has long been overlooked in foregoing
studies but is dominant in reality and is absolutely supramolecularly activated by 2:2
complexation of AC with βꢀCD. The intricate structural and photophysical aspects of this higherꢀ
order complexationꢀtriggered process were comprehensively elucidated, while the absolute
configurations of the slipped cyclodimers were unambiguously assigned by comparing the
experimental versus theoretical circular dichroism spectra. In the 2:2 complex, two ACs packed
in a dual βꢀCD capsule are not fully overlapped with each other but only partially stacked in
slipped anti- or syn-HT manner, and hence do not spontaneously cyclodimerize upon
photoexcitation but emits longꢀlived excimer fluorescence at wavelengths slightly longer than
the monomer fluorescence, indicating that the slipped excimer is neither extremely reactive nor
completely relaxed in conformation and energy. Due to the slipped conformation of the AC pair
in soft capsule, the subsequent photocyclodimerization becomes manipulable by various
internal/external factors, such as temperature, pressure, added salt, and host modification,
enabling us to exclusively obtain the slipped cyclodimers in high regioꢀ and enantioselectivities.
In this supramolecularly driven photochirogenesis, the dual βꢀCD capsule functions as a chiral
organophotocatalyst to trigger and accelerate the nonclassical photochirogenic route to slipped
cyclodimers by preꢀorganizing the conformation of encapsulated AC pair, formally mimicking
catalytic antibody.
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INTRODUCTION
Manipulating physical property and chemical reactivity of organic molecule through
noncovalent interaction is one of the most crucial goals in current photochemistry and
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supramolecular chemistry.
By forming supramolecular assembly, guest molecule(s) are
spatially confined, orientationally aligned, conformationally restricted, and locally concentrated
in a limited space of host cavity to alter the original properties and reactivities. Indeed, (chiral)
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molecular hosts, such as cyclodextrin, cavitand, cucurbituril, coordination cage, and
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hydrogenꢀbonding template, have been employed for controlling excitedꢀstate properties and
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reactivities through supramolecular assembling to achieve substantial changes in chiroptical
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1ꢀ8
property and stereochemical outcome in chirality sensing and photochirogenesis.
Anthracenes have long been a target of intensive photochemical research, which makes the
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photocyclodimerization of anthracenes one of the most established and utilized photoreactions.
Upon photoexcitation, anthracenes usually undergo the orbital symmetryꢀallowed [4+4]
cyclodimerization at 9,10ꢀpositions, whereas [6+6], [4+2], and [2+2] cyclodimerization, as well
1
0b,c
as slipped [4+4] cyclodimerization at 1,4ꢀ or 5,8ꢀpositions, rarely occur.
These
unconventional photocyclodimerization routes are occasionally triggered by the electronic and/or
1
1
steric effects of substituent(s) introduced to anthracene, but have never been activated by
supramolecular complexation.
A pioneering work on the supramolecular [4+4] photocyclodimerization of 1ꢀ, 2ꢀ, and 9ꢀ
anthracenecarboxylate and 1ꢀ and 2ꢀanthracenesulfonate mediated by
β
ꢀ and
γꢀcyclodextrin (CD)
1
2
was reported by Tamaki et al. in midꢀ1980s. They found that
γꢀCD greatly accelerates the
photocyclodimerization of 2ꢀanthracenecarboxylate and 1ꢀ and 2ꢀanthracenesulfonate as a result
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of the simultaneous inclusion of two anthracene guests in a
γꢀCD cavity. Of particular interest,
they reported that ꢀCD also accelerates the photocyclodimerization of 2ꢀanthracenecarboxylate
β
and ꢀsulfonate to preferentially afford anti-head-to-tail(antiꢀHT)ꢀ9,10:9',10'ꢀcyclodimer, without
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mentioning about the formation of any irregular cyclodimers.
In our further attempts to reinvestigate the photocyclodimerization of 2ꢀanthraceneꢀ
1
2
13,14
carboxylate (AC) mediated by
β
ꢀCD from the photochirogenic viewpoint,
we revealed that
β
ꢀCD not merely shifts the product selectivity to antiꢀHTꢀ9,10:9',10'ꢀcyclodimer 1 but
unexpectedly activates the nonclassical reaction pathway to slipped antiꢀ and synꢀHTꢀ5,8:9',10'ꢀ
cyclodimers 5 and 6 (Scheme 1). In this work, we first elucidate the chemical structures and
absolute configurations of these new chiral 5,8:9',10'ꢀcyclodimers, as well as the complexation
and photocyclodimerization mechanisms. Then, we will demonstrate that the present
supramolecular photochirogenic system, involving 2:2 complex, is highly susceptive to and
hence readily manipulable by various environmental factors and host modification to achieve the
exclusive formation of the slipped cyclodimers in high enantioselectivities. Finally, we will
discuss the origin and significance of this unique supramolecular photochirogenic reaction driven
by higherꢀorder complexation in a wider perspective of organocatalysis and catalytic antibody.
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Scheme 1. Supramolecular 1:1 and 2:2 Complexation of 2ꢀAnthracenecarboxylate (AC) with
Native
βꢀCyclodextrin (βꢀCD) and its Cationic Derivatives (7ꢀ12) and Subsequent
Photocyclodimerization to Classical 9,10:9',10'ꢀCyclodimers 1ꢀ4 and Nonclassical 5,8:9',10'ꢀ
Cyclodimers 5 and 6
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RESULTS AND DISCUSSION
Slipped 5,8:9',10'-Cyclodimers 5 and 6. Photoirradiation of AC (0.2 mM) with
βꢀCD (4
mM) was performed in phosphate buffer solution (PBS) at pH 9. The irradiated sample was
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subjected to chiral HPLC analysis to reveal the formation of unidentified photoproducts in
addition to conventional cyclodimers 1-4. Under the HPLC conditions employed, these new
products started to elute immediately after cyclodimer 4 and spread over a wide range of
1
5
retention time; see Figure S1 for the chiral HPLC traces monitored by serial circular dichroism
and fluorescence detectors. Crucially, the circular dichroism monitoring showed that the four
new peaks are assignable to the enantiomer pairs of two chiral products, while the fluorescence
monitoring at 420 nm with excitation at 340 nm (where 1ꢀ4 are transparent and hence
fluorometrically silent) implied that these new products carry a naphthalene chromophore. HPLC
1
5
analysis of the sample on achiral ODS column showed two major peaks (Figure S2), which
1
5
were collected separately to provide pure 5 (4.5% yield) and 6 (3.0% yield) (Figure S3; see also
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5
Figure S4 for the separation of enantiomers). Cyclodimer 6 was totally stable at least for 12
days in the eluent stored at room temperature in the dark, showing no appreciable changes upon
HPLC examinations before and after the storage; sharing the same skeleton, cyclodimer 5 is
expected to behave similarly.
15
MS spectra of 5 and 6 showed the molecular ion peaks at m/z 443 (Figures S5 and S6),
1
13
indicating that they are also AC dimers isomeric to 1ꢀ4. H and C NMR spectra of 5 and 6
closely resemble to each other (Figure 1; also compare Figure S9 with S10 and Figure S13 with
1
5
1
15
S14). In the H NMR spectra (Figures 1 and S7ꢀS10), 14 aromatic and 4 nonaromatic proton
signals were observed for both 5 and 6, while two nonequivalent carboxylic and 24 aromatic
1
3
15
carbons in the C NMR spectra (Figures S11ꢀS15), revealing the unsymmetrical nature of 5
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and 6. In addition, the four aromatic proton singlets observed indicate that the central aromatic
ring of one AC moiety is preserved in the cyclodimers.
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Figure 1. H NMR spectra of 5 and 6 in DMSOꢀd at 25 °C.
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To elucidate the structures of 5 and 6, several 2D NMR techniques were employed (Figures
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5
S16ꢀS37). Thus, the HSQC spectra were obtained to assign the protonated carbon resonances,
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while the coupling network of neighboring protons was elucidated by Hꢀ H COSY. By
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combining the results obtained by longꢀrange protonꢀcarbon correlation Hꢀ C HMBC and
NOESY, the quaternary carbons and the relative positions of all carbons and protons were
unequivocally assigned, allowing us to determine the structures of 5 and 6 as antiꢀ and synꢀHTꢀ
5
,8:9',10'ꢀcyclodimers (Scheme 1), respectively.
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The structural similarity of 5 and 6 led to the nearly superimposable UVꢀvis spectra over the
entire range (Figure 2, solid lines). In comparison to classical cyclodimers 1 and 3, slipped 5 and
6, possessing a naphthalene chromophore, absorb at much longer wavelengths; the 0ꢀ0 transition
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of the lowestꢀenergy L band is bathochromically shifted by 9.2 nm relative to that of
b
unsubstituted 2ꢀnaphthoate (Figure 2, dashed line). On the other hand, the UVꢀvis spectra of 5
and 6 in the highꢀenergy region are not a simple summation or average of those of 9,10:9',10'ꢀ
cyclodimer and 2ꢀnaphthoate, suggesting strong electronic interactions between the facing
naphthalene and benzene chromophores.
Figure 2. UVꢀvis spectra of cyclodimers 1 (cyan), 3 (black), 5 (red) and 6 (blue) and reference 2ꢀ
naphthoate (green) in alkaline methanol (NaOH) at 25 °C.
Chiroptical Properties and Absolute Configurations of Enantiomeric 5,8:9',10'-
Cyclodimers 5 and 6. Slipped cyclodimers 5 and 6 were resolved by preparative chiral HPLC to
1
5
give optically pure enantiomer pairs of 5 /5 and 6 /6 (Figure S4), where the subscripts +/ꢀ are
+
-
+
-
tentative tags to identify the first/second fractions eluted from the chiral column employed (OJꢀ
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RH). As shown in Figure 3, antiꢀ and synꢀisomeric 5 and 6 gave analogous UVꢀvis but distinctly
different circular dichroism spectra. The enantiomer pairs exhibited mirrorꢀimaged circular
ꢀ3
dichroism spectra with relatively large anisotropy factors (g = ꢀε/ε) of 2ꢀ4 x 10 at the main
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band, presumably due to the rigid skeleton that fixes the transition moments of neighboring
chromophores at defined angles.
30000
UV
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CD
3
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ε
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CD
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ꢀ
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g factor
g factor
0
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.004
.002
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200
00
240
280
320
360
240
280
320
360
Wavelength / nm
Wavelength / nm
Figure 3. UVꢀvis (top), circular dichroism (middle), and anisotropy (g) factor (bottom) spectra
of enantiopure 5 (10.2
ꢁM) (green), 5- (8.3
ꢁ
M) (magenta), 6 (3.8
ꢁM) (red), and 6- (3.5
ꢁM)
+
+
(blue) in PBS (pH 9.0) at 25 °C.
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1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
The absolute configurations of 5 /5 and 6 /6 were determined by comparing the
+
-
+
-
experimental circular dichroism spectra with the theoretical simulations at the RIꢀCC2/def2ꢀ
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
16
TZVPP level. As can be seen from Figure 4, the experimental circular dichroism spectrum of
5+
is in good agreement with the theoretical spectrum calculated for (5S,8R:9'S,10'R)ꢀ5, and the
experimental spectrum of 6 agrees with the theoretical one calculated for (5S,8R:9’S,10’R)ꢀ6;
+
15
for the optimized geometries, see Tables S1 and S2.
8
0
0
0
4
0
0
0
4
2
ε
ꢀ
ε
ꢀ
ꢀ
ꢀ
40
80
ꢀ20
200
250
300
350
200
250
300
350
Wavelength / nm
Wavelength / nm
Figure 4. Experimental CD spectra of firstꢀeluted 5 (green) and 6 (red) measured in PBS, on
+
+
which overlaid are the theoretical spectra calculated for (5S,8R:9'S,10'R)ꢀ5 and (5S,8R:9’S,10’R)ꢀ
at the RIꢀCC2/TZVPP level (redꢀshifted by 0.3 eV) (gray), respectively.
6
1
Higher-Order Complexation of AC with
β-CD. Variable temperature H NMR spectra of
AC (2 mM) were recorded in the presence of ꢀCD (4 mM) in a D O solution at pD 9.0 (Figures
β
2
1
5
5 and S38). As shown in Figure 5, by lowering the temperature from 50 to 5 °C, AC’s H5ꢀH8
protons located farthest from the carboxylate greatly shifted to the upfield by 0.47ꢀ1.21 ppm with
accompanying peak broadening, while H9 and H10 exhibited much smaller upfield shifts of
0
.07ꢀ0.17 ppm and the H1, H3, and H4 near the carboxylate showed no practical shifts. Thus, the
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degree of upfield shift decreased in the order: H6 > H7 > H5 > H8 >> H9 > H10 >> H4 > H3 and
H1, indicating partial overlap of the two included AC molecules at the far edge (from the
carboxylate). This trend significantly differs from that observed for the 2:1 complexation of AC
1
3a
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
with γꢀCD, where all of the aromatic protons experience large upfield shifts due to the full
stacking of two AC molecules in the cavity. The magnitudes of chemical shift changes observed
upon VTꢀNMR nicely correlate with the population of 2:2 complex that increases with deceasing
temperature (Figure 5, right column).
1
Figure 5. VT H NMR spectra of AC (2 mM) with
β
ꢀCD (4 mM) in a phosphateꢀbuffered D O
2
solution (pD 9.0) at 50, 35, 20, and 5 °C; the molar population of free AC, 1:1, and 2:2 complex
at each temperature was calculated by using the thermodynamic parameters shown in Table 1
(vide infra).
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2
2
2
2
2
2
2
2
2
3
3
3
3
3
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3
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3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
The orientation of included AC in
β
ꢀCD cavity was elucidated by using the ROESY
technique. As shown in Figure 6, the H5’ proton on the interior wall near the primary rim of βꢀ
CD gave crosspeaks with AC’s H1, H3, and H4, as well as H9 and H10, while H3’ located near
the secondary rim of ꢀCD only correlated with H8 (weak), H9, and H10. Crucially, no clear
crosspeaks were observed between H5ꢀH7 of AC and H3’ or H5’ of ꢀCD, partially due to the
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
β
β
peak broadening. These ROESY results unequivocally indicate that the carboxylateꢀbearing
benzene ring of AC is oriented toward the primary rim and positioned in between H3’ and H5’ of
β
ꢀCD, while the central ring is located near the secondary rim, leaving the terminal ring outside
the cavity (Figure 6, inset). Combining the ROESY results with the aboveꢀmentioned stronger
shielding effects observed particularly for H5ꢀH8 on the terminal ring at lower temperatures, we
conclude that the 2:2 complex is formed through the association of two 1:1 complexes from the
secondary rim, where the terminal aromatic ring of AC is somewhat exposed to facilitate further
assembly to the 2:2 complex through πꢀπ stacking. It is likely therefore that the formation of 1:2
or 2:1 complex is not feasible, and free AC and 1:1 and 2:2 complexes become the major species
in the solution. As can be seen from the VTꢀNMR spectra (Figure 5), the 2:2 complex is a minor
species at higher temperatures but rapidly grows in population by lowering the solution
temperature.
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5
6
0
1
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5
6
7
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9
0
1
2
3
4
5
6
7
8
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1
2
3
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6
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9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 6. Partial ROESY spectrum of a phosphateꢀbuffered D O solution (pD 9.0) of AC (2 mM)
2
and βꢀCD (4 mM) at 25 °C and the estimated position of AC in the CD cavity (inset). Under the
conditions employed, the population of free AC, 1:1 complex, and 2:2 complex is 8:66:26, and
hence the crosspeaks are considered to arise from both the complexes.
For better illustrating the stacking geometry of 2:2 complex, we performed the molecular
modeling study using the dispersionꢀcorrected DFT method at the DFTꢀD3(BJ)ꢀTPSS/def2ꢀ
1
8
SV(P) level to obtain the structures simulated for the re-re, si-si, and re-si complexes. As can
1
5
be seen from Figure S39, two AC molecules are stacked to each other but sled by one to oneꢀ
andꢀaꢀhalf benzene units, which is in good agreement with the position of AC in the βꢀCD cavity
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2
2
2
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3
3
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4
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4
4
4
4
4
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5
5
5
5
5
5
5
5
5
5
6
estimated from the NMR ROESY study (Figure 6). It is also to note that the two βꢀCDs are held
together by a hydrogenꢀbonding network interweaving the facing βꢀCD’s secondary rims.
To quantitatively evaluate the complexation of AC with
βꢀCD, we performed the UVꢀvis
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
and circular dichroism spectral titrations in PBS at 25 °C. As shown in Figure 7a, addition of
β
ꢀ
1
1
CD to a solution of AC (0.2 mM) induced small bathochromic shifts of the B and L bands of
b
a
AC with accompanying isosbestic points, suggesting less extensive stacking interaction. This
issue will be discussed later in relation to the excimer fluorescence.
2 0 0
2 5 0
3 0 0
3 5 0
4 0 0
4 5 0
5 0 0
W a v e le n g th / n m
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8
6
4
2
0
(
c)
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
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4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
θ
ꢀ
0
.0 0.5 1.0 1.5 2.0 2.5
[βꢀCD] / mM
Figure 7. (a) UVꢀvis and (b) circular dichroism spectral changes of AC (0.2 mM) upon titration
with ꢀCD (0ꢀ2 mM) in PBS (pH 9.0) at 25 °C; measured in a 1 mm cell. (c) Nonlinear least
β
squares fit of the ellipticity changes (ꢀθ) at 258 nm, assuming the stepwise 1:1 and 2:2
complexation.
In the circular dichroism spectral titration (Figure 7b), gradual addition of
β
ꢀCD induced a
1
1
positive Cotton effect at the B band and a negative one at the L band. According to the
b
a
19
empirical “sector rule” proposed by Kajtár et al., these induced Cotton effect signs indicate that
AC longitudinally penetrates into the CD cavity as illustrated in Figure 6, where the longitudinal
1
1
B and transversal L transitions are respectively aligned parallel and orthogonal to the CD axis.
b
a
The UVꢀvis spectral Job plots obtained at 0.5 °C for the solutions of AC and βꢀCD at a fixed
1
5
total concentration of 0.2 mM (Figures S40ꢀS42) reached the maximum at molar fraction 0.5,
indicating formally n:n but practically 1:1 stoichiometry. The lack of a bisignate exciton couplet
in the circular dichroism spectrum (Figure 7b) did not appear to support the contribution of 2:2
complex at least at this low total concentration (0.2 mM). Nevertheless, the circular dichroism
1
5
spectral titration data (Figure 7b) did not fit to the simple 1:1 complexation model (Figure S43)
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1
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2
2
2
2
2
2
2
2
2
2
3
3
3
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4
4
4
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5
5
5
5
5
5
5
6
but were reasonably analyzed by assuming stepwise 1:1 and 2:2 complexation (equations 1 and
ꢀ1
2
), as shown in Figure 7c, to give a relatively large 1:1 association constant (K ) of 3800 M and
1
ꢀ1
20a
20b,c
a much smaller 2:2 association constant (K ) of 150 M . In this relation, Hamai and Bohne
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
have reported that βꢀCD similarly forms 1:1 and 2:2 complexes with naphthalene derivatives, but
the K values are much larger than the corresponding K values, leading to highly efficient 2:2
2
1
complexation. Crucially,
β
ꢀCD and 2ꢀanthracenesulfonate form 1:1 and 2:2 complexes with the
20a
K value larger than K , as is exactly the case with the present system (Table 1). This and our
1
2
present results indicate that the anthracene moiety provides strong hydrophobic interaction with
ꢀCD favorable for the 1:1 complexation but the steric bulk makes the 2:2 complexation less
favorable.
β
K = [AC•
β
ꢀCD]/[AC][
β
ꢀCD]
(1)
(2)
1
2
K = [AC •βꢀCD ]/[AC•βꢀCD]
2
2
2
By using the K and K values obtained, the population of free AC, 1:1, and 2:2 complex
1
2
was calculated to be 12:84:4 for an aqueous solution containing 0.2 mM AC and 2.0 mM βꢀCD
at 25 °C. This low molar population (4%) of the 2:2 complex even at the highest host
concentration employed in the titration experiment (Figure 7) may rationalize the apparent lack
of exciton couplet in the circular dichroism spectra. Similar titration experiments at 0.5 and
1
5
50 °C (Figure S44) and the subsequent fitting of the titration data to equations 1 and 2 (Figure
1
5
S45) gave the K and K values at these temperatures, as listed in Table 1.
1
2
Table 1. Thermodynamic Parameters for the 1:1 and 2:2 Complexation of AC with
β
ꢀCD in PBS
at pH 9.0
−
1
a
stoichioꢀ temperaꢀ
CsCl/M
Κ/Μ
ꢀG°/
ꢀH°/
TꢀS° /
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ꢀ1
ꢀ1
ꢀ1
metry
ture/°C
50
kJ mol
kJ mol
kJ mol
1
:1
0
0
0
1900 ± 30
25
3800 ± 50
4400 ± 30
5500 ± 90
8500 ± 100
90 ± 10
ꢀ20.4 ± 0.1
ꢀ22.6 ± 0.1
ꢀ2.2 ± 0.1
.5
6.0
0
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
0
.5
.5
2
:2
50
0
2
5
0
0
150 ± 30
230 ± 10
300 ± 30
270 ± 30
ꢀ12.4 ± 0.5
ꢀ16.5± 0.1
ꢀ4.1 ± 0.1
0
.5
6.0
0
a
T = 298 K.
ꢀ
1
The K value of 3800 M obtained for AC at 25 °C is reasonable as an association constant
1
ꢀ1
with
β
ꢀCD, when compared with those for benzoate (K = 16 M ) and 2ꢀnaphthoate (K = 320
1
1
ꢀ1
21
ꢀ1
M ). The much smaller K value of 150 M , although no corresponding values have been
2
reported for the lower homologues, is also sensible if the limited extra space remaining in the 1:1
complex and the partial πꢀoverlap at the farꢀedge of AC are taken into consideration. For a better
thermodynamic understanding of the 1:1 and in particular the 2:2 complexation, the association
constants at different temperatures (Table 1) were subjected to the van’t Hoff analyses to give
15
straight lines for both the stoichiometries (Figure S46), from the slope and intercept of which
the enthalpy (ꢀH°) and entropy (ꢀS°) changes upon 1:1 and 2:2 complexation were calculated as
listed in Table 1. The thermodynamic parameters thus obtained indicate that both the 1:1 and 2:2
complexation are obviously enthalpyꢀdriven with much smaller entropic losses. The significantly
smaller free energy of complexation for the 2:2 complexation (ꢀꢀG° = ꢀG°1:1 ꢀ ꢀG°2:2 = ꢀ8.0 kJ
ꢀ1
ꢀ1
mol ) is traced back mainly to the smaller enthalpic gain (ꢀꢀH° = ꢀ6.1 kJ mol ) and somewhat
ꢀ1
to the larger entropic loss (TꢀꢀS° = 1.9 kJ mol ), the former of which would be attributable to
the less extensive hydrophobic and
π
ꢀstacking interactions and the latter to the repositioning of
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1
2
2
2
2
2
2
2
2
2
2
3
3
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AC guest in the CD cavity upon assembling two 1:1 complexes. These thermodynamic
parameters also allow us to calculate the population of free and complexed AC species at any
concentration and temperature. Thus, the significant NMR upfield shifts of H5ꢀH8 protons in AC
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(Figure 5) are reasonably accounted for in terms of the population of the 2:2 complex enhanced
to 36% in a solution containing 2 mM AC and 4 mM ꢀCD at 5 °C.
β
Fluorescence Spectral Studies. The excitedꢀstate properties of AC‒
first examined by fluorescence spectroscopy. In the absence of ꢀCD, AC (2
fluorescence at 426 nm in PBS (Figure 8a, red) without showing any sign of excimer
fluorescence at longer wavelengths. However, when ꢀCD (5 mM) was added to this solution,
β
ꢀCD complexes were
β
ꢁM) emitted broad
β
the AC fluorescence was appreciably reduced in intensity and exhibited vibrational fine
structures (Figure 8a, blue), indicating inclusion of AC in the hydrophobic CD cavity. Under the
conditions employed, the population of 2:2 complex was calculated as negligible 0.05% (while
those of free AC and 1:1 complex were 5.00% and 94.95%, respectively), and hence the
spectroscopic changes were reasonably attributed to the 1:1 complexation.
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Figure 8. (a) Fluorescence spectra of AC (2
CD (5 mM) in PBS (pH 9.0) at 25 °C; λex 327 nm. (b) Normalized (in the short wavelength
region below 393 nm) fluorescence spectra of AC at 2 M (blue) and 200 M (red) in the
presence of ꢀCD (5 mM) in PBS (pH 9.0) at 25 °C (λex 327 nm) and the fluorescence spectrum
ꢁM) in the presence (blue) and absence (red) of βꢀ
ꢁ
ꢁ
β
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
of the excimer formed in the 2:2 complex, which was estimated by the spectrum subtraction of
the former from the latter.
In contrast, a solution containing 100ꢀfold more concentrated AC (200
ꢁM) and comparable
concentration of ꢀCD (5.2 mM) exhibited broader fluorescence with a tail extended to longer
β
wavelengths (Figure 8b, red). The fluorescence spectra at high and low AC concentrations are
normalized in the shortꢀwavelength region and subtracted to give a difference spectrum shown in
Figure 8b (green broken line), which is considered to be the excimer fluorescence from 2:2
complex, the population of which amounts to 4.8% (meaning that 9.2% of the incident light is
absorbed by the dimeric species) under the conditions employed; the remainders are free AC
(4.7%) and the 1:1 complex (90.5%); see Table 2. Excimer fluorescence of anthracene has rarely
been observed in solution due to the rapid radiative and nonꢀradiative decays through
fluorescence and photocyclodimerization. Nevertheless, ACs tethered to a diol scaffold are
known to form a frustrated excimer, which is sterically hindered from cyclodimerization and
2
2
hence fluoresces at wavelengths slightly longer than the monomer emission. In the present case,
the photocyclodimerization is thought to be supramolecularly decelerated by confining the pair
of ACs in a dual βꢀCD capsule.
The fluorescence excitation spectra of a 2
ꢁM AC solution containing 5 mM βꢀCD
monitored at 400 and 500 nm (Figure 9a) were practically superimposable with each other. In
contrast, the excitation spectrum of a 200
ꢁM AC solution with 5.2 mM
βꢀCD monitored at 500
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5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
nm significantly deviated to longer wavelengths from that monitored at 400 nm and also from
the UVꢀvis spectrum (Figure 9b). This is attributed to the bathochromic shift of AC (200 ꢁM) in
the UVꢀvis spectrum due to the partially stacked ACs in 2:2 complex (Figure 7). These results
clearly indicate that the emission at longer wavelengths originates from the excitation of groundꢀ
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
state AC dimer partially stacked in a βꢀCD capsule.
(a)
(b)
Figure 9. (a) Normalized excitation spectra of AC at 2
monitored at 400 (orange) and 500 nm (green); (b) normalized excitation spectra of AC at 200
M in the presence of ꢀCD (5.2 mM), monitored at 400 (orange) and 500 nm (green), and UVꢀ
ꢁM in the presence of βꢀCD (5.0 mM),
ꢁ
β
vis spectrum (dotted cyan); all in PBS (pH 9) at 25 °C.
This conclusion is reinforced by the result of fluorescence lifetime measurements. AC (2
ꢁ
M) in PBS gave a single fluorescence lifetime ( 1
wavelength employed (Table 2, top two lines). Upon addition of
solution, the decay profile became a sum of two exponential functions of τ1 = 16.9 ns and τ2
0.9ꢀ11.2 ns, the latter of which was assigned to the excited 1:1 complex dominating with
relative abundance (A ) of 89% at 400 nm and 68% at 500 nm. The smaller A value obtained
τ
) of 16.9 ns, irrespective of the monitoring
β
ꢀCD (5 mM) to this dilute AC
=
1
2
2
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upon monitoring at 500 nm is attributable to the sharpening of the fluorescence spectrum upon
inclusion by βꢀCD (Figure 8a).
Table 2. Fluorescence Lifetimes of Free AC (τ1), 1:1 Complex (τ2), and 2:2 Complex (τ3)
a
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Determined at Different Concentrations and Monitoring Wavelengths
b
population /%
c
AC
β
ꢀCD
/mM
λem
τ1
τ2
τ3
2
A1
A2
A3
χ
free
1:1
2:2
/
ꢁM
/nm
/ns
/ns
/ns
AC complex complex
2
0
100
400
500
400
16.9
16.9
1.09
1.09
1.06
1.09
1.06
d
2
5.0
5.2
5.00 94.95
0.05
4.9
16.9
16.9
16.9
16.9
0.11 11.2
0.32 10.9
0.22 10.4
0.16 10.4
0.89
0.68
0.78
d
d
d
5
00
2
00
4.7
90.4
400
500
d
0.51 57.9
0.33 1.06
a
b
ꢀ1
ꢀ1
Measured in PBS (pH 9.0) at 25 °C: λex = 340 nm. Calculated by using K = 3800 M and K = 150 M
1
2
c
d
(
Table 1). Monitoring wavelength. Fixed value.
At the higher AC concentration (200 ꢁM), two species of τ1 = 16.9 ns and τ2 = 10.4 ns were
similarly observed when monitored at 400 nm, but a new much longerꢀlived species of τ3 = 57.9
ns emerged in addition to the above two species when the fluorescence was monitored at 500 nm
15
(
Figure 10a and Table 2, bottom lines, see also Figure S47). It is to note that the decay profile
was successfully analyzed without involving a rise, implying that the formation of 2:2 complex
1
5
is not an excitedꢀstate but a groundꢀstate event. As shown in Figures 10b and S48, the timeꢀ
resolved fluorescence spectra taken at 1, 10, 30, and 50 ns after excitation revealed that the highꢀ
energy fluorescence from the excited 1:1 complex decays rapidly to leave a longꢀlived broad
fluorescence that resembles in shape the steadyꢀstate excimer fluorescence obtained by the
spectrum subtraction (Figure 8b). We therefore assigned this redꢀshifted, longerꢀlived
structureless emission to the excimer fluorescence from the slipped AC pair in a 2:2 complex.
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 10. (a) Fluorescence decay profiles of AC (200
ꢁM) in the presence of βꢀCD (5.0 mM) at
2
5 °C, monitored at 400 nm (purple) and 500 nm (red); λex 280 nm. (b) Timeꢀresolved
fluorescence spectra at 1 (blue), 10 (red), 30 (cyan), and 50 ns (green) after excitation.
Upon excitation in fluid solution, anthracene derivatives usually emit monomer fluorescence
or undergo photocyclodimerization, and no excimer fluorescence is observed even at low
temperatures. Ferguson and coworkers, however, have demonstrated that an anthracene pair
generated by photosplitting anthracene cyclodimer gives an emissive excimer in rigid matrices at
2
3
7
7 K. Ramamurthy et al. have observed the excimer fluorescence of a pair of unsubstituted
anthracenes (AN) confined in an octa acid (OA) capsule in aqueous solution at room temperature,
4
b
where the photocyclodimerization is completely suppressed. The confinement of two AN
molecules in a rigid OA capsule of slow assembling/disassembling dynamics and the sterically
hindered photocyclodimerization in a narrow capsule are jointly responsible for this
unprecedented observation of excimer fluorescence in solution.
The present excimer generated by the excitation of a 2:2 complex of AC with
βꢀCD
(
[AC2• -CD ]*) differs in photophysical and photochemical behavior from the AN excimer
β
2
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confined in OA capsule ([AN •OA ]*). Thus, the Stokes shift of excimer fluorescence is much
2
2
smaller for [AC2•β-CD ]* than for [AN •OA ]* and the lifetime is also significantly shorter for
2 2 2
4
b
the former (60 ns) than for the latter (263 ns). More crucially, [AC •
β
-CD ]* can cyclodimerize
2
2
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
to regular 9,10:9',10'ꢀ and slipped 5,8:9',10'ꢀcyclodimers (Scheme 1). All of these unusual
photophysical and photochemical behaviors are attributable to the slipped arrangement of two
ꢀ1
ACs accommodated in a weakly bound dual
β
ꢀCD capsule (K = 150 M at 25 °C), which allows
2
the slipped excimer to competitively fluoresce with a small Stokes shift and cyclodimerize in
both regular and irregular manners in a readily disassembling soft capsule.
Photocyclodimerization Kinetics. The overall photocyclodimerization rate was determined
at 25 °C for a PBS solution of AC (0.2 mM) in the presence and absence of
βꢀCD (2 mM) by
monitoring the UVꢀvis spectral changes upon irradiation at 365 nm with LED. As shown in
1
5
Figures S49ꢀS52, the absorbance of AC smoothly decreased with increasing irradiation time
and the absorbance changes obtained in the presence and absence of ꢀCD were analyzed by
assuming the firstꢀorder and secondꢀorder kinetics, respectively, to give apparent rate constants
β
ꢀ1
ꢀ1 ꢀ1
ꢀ1
of k = 0.0236 ± 0.0003 s and k = 117 ± 4 M s (or k [AC] = 0.0234 s at [AC] = 0.2 mM).
1
2
2
The apparent rate acceleration by
β
ꢀCD may look essentially nil, being mere 1.01ꢀfold, but the
population of the 2:2 complex is only 4% at the host and guest concentrations employed; note
that the 1:1 complex of 84% population is practically photoinert, while free AC of 12%
population may undergo photocyclodimerization but its contribution to the overall rate is nearly
negligible due to the bimolecular nature of the reaction. Considering this population and the fact
that the 2:2 complex contains two AC molecules and hence has a twice larger absorbance than
free AC, we calculated the real acceleration as 13ꢀfold at this relatively low concentration of AC
(0.2 mM). This significant acceleration well rationalizes the dominant formation of 1, 5, and 6
derived from the less populated 2:2 complex.
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6
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
It would be interesting if the individual photocyclodimerization rate constants for re-re, re-si,
and si-si complexes (Scheme 2) could be estimated. However, this is hampered by the lack of
information about the population of these species in the solution (which should differ from the
product distribution, as the rate of subsequent photocyclodimerization is not the same for each
species). Nevertheless, we examined the time course of the photocyclodimerization of AC (0.2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
mM) in the presence of
βꢀCD (2.0 mM) at 25 °C by monitoring the UVꢀvis spectral changes
upon irradiation for up to 75 min. The yields of cyclodimers 1ꢀ6 were determined every 15 min
1
5
of irradiation by chiral HPLC (Figure S53). The product distribution was kept constant
throughout the irradiation, and the reaction obeyed the apparent firstꢀorder rate equation to give
the rate constant shown in Table S5 in SI. In a solution containing 0.2 mM AC and 2.0 mM βꢀ
CD, there exist free AC, 1:1, and 2:2 complexes in a 12:84:4 ratio, but decoupling the
contribution of re-re, re-si, and si-si complexes is not feasible and hence the individual rate
constants cannot be estimated. However, this experiment enabled us to confirm that the product
ratio does not vary at least up to 80% conversion, indicating the sole origin of the slipped dimers.
Diastereomeric 2:2 Complexation and Enantiomeric Photocyclodimerization
Mechanisms. We first consider the stereochemical aspects of the 2:2 complexation and
subsequent photocyclodimerization of the AC pair in a
βꢀCD capsule. Since prochiral AC
possesses the enantiotopic re and si faces, there exist four possible stereoisomeric 2:2 complexes:
re-si, si-re, re-re, and si-si (Scheme 2). The former two are stereochemically equivalent to each
other and photocyclodimerize either to achiral cyclodimer 1 or to chiral slipped cyclodimer 5. It
is worth mentioning that the excitation of either reꢀAC or siꢀAC in a re-si complex leads to
distinctly different stereochemical consequences, affording either re*ꢀsi or reꢀsi* complex,
which are diastereomeric to each other. On the other hand, the latter two (i.e., the re-re and si-si
complexes) are inherently diastereomeric in the ground and excited states and
photocyclodimerize to the corresponding enantiomer of cyclodimer 2 or slipped cyclodimer 6.
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8
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Scheme 2. Photocyclodimerization of Diastereomeric 2:2 Complexes to Regular 9,10:9',10'ꢀ
Cyclodimers (1 and 2) and Slipped 5,8:9',10'ꢀCyclodimers (5 and 6) in a βꢀCD Capsule
a
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a
Re-si and si-re complexes are equivalent to each other in the ground state but photoexcitation of reꢀ or
siꢀAC in a re-si (or si-re) complex breaks the centrosymmetric nature of two facing ACs to render the
resulting re*-si or re-si* complex diastereomeric. On the other hand, the re-re and si-si complexes are
inherently diastereomeric to each other in both ground and excited states.
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
As illustrated in Scheme 2 (top branching equation), when a re-si (or si-re) complex
photocyclodimerizes at the 9,10ꢀpositions, achiral 1 is formed. If the photocyclodimerization
occurs between the siꢀAC’s 5,8ꢀpositions and the reꢀAC’s 9,10ꢀpositions, slipped
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
5R,8S:9'R,10'S)ꢀ5 is produced, while the reaction between the reꢀAC’s 5,8ꢀpositions and the siꢀ
AC’s 9,10ꢀpositions leads to antipodal (5S,8R:9'S,10'R)ꢀ5. In the case of synꢀHT complex
Scheme 2, bottom two equations), the diastereomeric re-re and si-si complexes respectively
(
afford enantiomeric (9S,10R:9'S,10'R)ꢀ and (9R,10S:9'R,10'S)ꢀ2 upon 9,10:9',10'ꢀ
cyclodimerization and also slipped (5S,8R:9'S,10'R)ꢀ and (5R,8S:9'R,10'S)ꢀ6 upon 5,8:9',10'ꢀ
cyclodimerization. Since neither the reꢀequilibration among the excited complexes nor the
swapping of two ACs in the narrow cavity of a βꢀCD capsule is expected to occur within the
short lifetimes (vide supra), the chemical and optical yields of each product are determined by
the groundꢀstate thermodynamics (i.e., the population of free AC and 1:1 and 2:2 complexes) and
the excitedꢀstate kinetics (i.e., the photocyclodimerization efficiency of relevant complexes),
both of which can be manipulated by the host/guest ratio, the excitation wavelength, and the
environmental variants, such as temperature, pressure, and solvent conditions.
Enantiodifferentiating Photocyclodimerization of AC with
Ratio and Temperature. To quantitatively discuss the photochemical and stereochemical
consequences of the 2:2 complexation, the effects of ꢀCD concentration and temperature on the
β-CD: Effects of Host/Guest
β
chemical and optical yields of slipped cyclodimers 5 and 6 were first examined. Table 3 lists the
population of free AC, 1:1, and 2:2 complexes in the solutions of AC (0.2 mM) in PBS (pH 9) at
various
βꢀCD concentrations (0ꢀ5.2 or 0ꢀ11.4 mM) and temperatures (50, 25, and 0.5 °C), and
also the chemical yields and enantiomeric excesses (ee’s) of regular cyclodimers 1ꢀ4 and slipped
5
and 6 obtained upon photoirradiation of the solutions; for the full results, see Table S3.
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a
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
Table 3. Enantiodifferentiating Photocyclodimerization of AC Mediated by native
β
ꢀCD in PBS at Various Host/Guest Ratios and Temperatures
b
d
population /%
1:1 2:2
AC complex complex
yield/%
ee /%
T/ AC
mM /mM
β
ꢀCD
irradiaꢀ converꢀ
tion/h sion /%
(1+5)
/(2+6)
5/1 6/2
free
c
/
°C
1
2
3
4
5
6
2
3
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
5
0
0.2 0.6 51.2
48.0
0.8
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
50
55
55
46
37
38
43
57
39
26
37
95
42
47
60
61
40
42
50
59
65
59
64
65
65
62
26
4
13
3
7
5
2
1
ꢀ1
ꢀ1
ꢀ3
0
40
41
37
f
37 0.11 0.06 1.9
31 0.38 2.1 6.3
26 0.41 3.3 7.7
5.2
9
5
88
3
1
e
23
25
0
9
9
0
1
2
6
8
5
8
8
8
9
ꢀ8
ꢀ12
0
11.4
0
92
3
3
2
2
5
0.2
100
0
0
34
31
24
8
16
15
10
4
10
9
f
0
0
1.2
0
0
0
.1 80.8
.2 66.0
.6 35
19.0
33.3
63
0.2
0.7
2
2
ꢀ1
0
46
48
45
47
43
44
43
44
43
31 0.06 0.02 1.4
34 0.15 0.09 2.1
32 0.34 0.79 5.5
24 0.39 6.0 9.2
15 0.29 0.5 5.0
17 0.38 3.1 8.8
16 0.39 8.1 10.0
17 0.40 8.0 10.1
7
7
ꢀ1
ꢀ1
0
3
20
25
17
24
26
26
29
ꢀ5
5.2
5
90
5
1
1
e
ꢀ10
ꢀ4
ꢀ1
ꢀ1
ꢀ5
g
0
.5 0.2 0.2 53.3
45.9
74
0.8
6
10
2
5
4
0
5
.6 20
1
1
ꢀ14
ꢀ18
ꢀ18
ꢀ17
.2
2
89
9
1
e
e
2
.0
1
e
e
g
0.6 5.2
2
78
20
0.5
e
e
e
g
15 0.47 >20
10.6
a
b
PBS solutions (pH 9.0) of AC and βꢀCD were irradiated at 390 nm with a 300W xenon lamp through an interference filter (bandwidth = 10 nm).
Calculated from the K and K values obtained experimentally or extrapolated by using the thermodynamic parameters in Table 1. Consumption of
AC determined by UVꢀvis monitoring at 388 nm. Enantiomeric excess determined by chiral HPLC, where the firstꢀeluted enantiomer is given a
positive sign for all of the chiral products, i.e., 2, 3, 5, and 6; error in ee < 2%. Yield < 0.5%. Not applicable. Not determined due to low yield.
c
1
2
d
e
f
g
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2
2
2
2
2
2
2
2
2
3
3
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3
4
4
4
4
4
4
4
4
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4
5
5
5
5
5
5
5
5
5
5
6
In the absence of
β
ꢀCD, the photoirradiation of AC (0.2 mM) for 30 min at 25 °C led to a
4
6% conversion and the dominant formation of 1 and 2 in 74% combined yield. This HTꢀ
preference is attributable to the electrostatic and steric repulsions of the carboxylate anions in
two reacting ACs. Notably, no irregular dimers were detected. Upon addition of 0.1ꢀ5.2 mM
CD at 25 °C, the conversion of AC was first reduced to 37% at 0.1 mM ꢀCD but then gradually
increased to reach 57% at the highest host concentration. The initial reduction and the rather
slow growth of conversion thereafter are sensible, since the 1:1 complexation with ꢀCD blocks
the photocyclodimerization of included AC. It should be noted however that even a
substoichiometric amount of ꢀCD (0.1 mM), with the population of 2:2 complex at mere 0.2%
Table 3), is sufficient to turn on the slipped photocyclodimerization to 5 and 6 and their ee’s are
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
β
ꢀ
β
β
β
(
comparable to those obtained at higher host concentrations, indicating the catalytic nature of the
higherꢀorder complex. Thus, under the condition of K < K , the system can be catalytic because
2
1
the dissociation is likely to be faster for the weakly bound 2:2 complex than for the stronger 1:1
complex, enabling the latter to serve as a reservoir for the catalytic precursor complex, while the
release of the volumeꢀexpanded product cyclodimer from the
βꢀCD capsule should be
spontaneous. Such a situation will enhance the turnover of the catalytic cycle.
The chemical yield change was more straightforward as a function of host concentration.
When the concentration of βꢀCD was increased to 5.2 mM, cyclodimers 2ꢀ4 almost disappeared
and 1, 5, and 6 became dominant (98% combined yield at 57% conversion). This dramatic
switching of product selectivity, as well as the gradually increasing conversions mentioned
above, are directly related to the enhanced population of 2:2 complex, which is still low (5%)
even at the highest host concentration but greatly expedites the subsequent
photocyclodimerization to dominate the overall photochemistry. Since both 1 and 5 are derived
28
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Page 29 of 49
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
from the anti-HT (re-si and si-re) complexes while 2 and 6 from the syn-HT (re-re and si-si)
complexes (Scheme 2), the anti/syn preference upon complexation and photocyclodimerization
can be evaluated by the (1+5)/(2+6) ratio. As shown in Table 3, the anti/syn preference rapidly
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
increases from 1.2 to 9.2 as the concentration of
βꢀCD increases from 0 to 5.2 mM. The
thermodynamically favored antiꢀHT complexation and the kinetically expedited
photocyclodimerization are most likely responsible for this trend. In contrast, the 5/6 ratio is kept
constant at around 3 over the entire concentration range employed, indicating the single origin,
i.e. the 2:2 complex. It is also interesting that the antiꢀHT complex favors the
photocyclodimerization to regular 9,10:9',10'ꢀcyclodimer 1 with a 5/1 ratio of 0.39 at 5.2 mM
CD, whereas the synꢀHT complex predominantly photocyclodimerizes to 6 with a 6/2 ratio of 6.0
at the highest ꢀCD concentration. This is probably because the synꢀHT complexation is
βꢀ
β
inherently less favored (as judged from the (1+5)/(2+6) ratio as high as 9.2) and the 9,10:9',10'ꢀ
photocyclodimerization of two ACs in the synꢀHT complex, requiring deeper mutual penetration
into the βꢀCD cavity, is sterically more demanding and less favored.
The enantiomeric excess (ee) of 2 was consistently low (<10%) at 25 °C, while those of
slipped cyclodimers 5 and 6 were much higher at 43ꢀ48% and 24ꢀ34%, respectively. More
crucially, the ee values for 5 and 6 did not vary with the host or AC concentration or the
irradiation time of up to 2 h to achieve a 95% conversion (Table 3), supporting the above
conclusion that the slipped cyclodimers originate solely from the 2:2 complex. The crucial role
of photocyclodimerization kinetics was revealed by the inconsistent ee values obtained for 2
versus 6. If the diastereomeric re-re and si-si complexes spontaneously cyclodimerized upon
irradiation at the same rate, the ee’s of the cyclodimers would be determined exclusively by the
groundꢀstate population of the re-re and si-si complexes (Scheme 2). Also, the ee’s of 2 and 6
29
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