Organic Letters
Letter
structure of CDx derivatives, the product distributions and
enantioselectivities were also critically affected by various
external factors such as solvent, temperature, pressure,
irradiation wavelength, and additives.4,5,10 In the present
work, we explored the pH effect on the photocyclodimeriza-
tion of AC mediated by native and modified γ-CDx 5−
8 (Figure 1), and demonstrated that pH played a vital role in
photocyclodimerization of AC even to cause an inversion of
product chirality.
Table 1. Association Constants for the 1:1 and 1:2 Host−
a
Guest Complexation of 7 with AC
Association Constant [M−1
]
pH
K1
K2
K1 K2 [× 107 M−2
]
K2/K1
6.0
7.0
8.0
9.0
1410 290
3370 200
4340 240
3680 350
15800 2300
11700 780
10900 650
8650 840
2.23
3.94
4.73
3.18
11.2
3.5
2.5
2.4
a
ITC measurements in PBS of different pH at 25 °C.
from CDx cavity or exchange their arrangements during the
short excited-state lifetime (16 ns). Interestingly, the
association constants of 7 with AC showed clear pH-
dependence (see Table 1). Upon increasing the pH from 6
to 9, the K1 value was significantly enhanced, while K2 were
markedly decreased. The ratio of K2/K1 was given in the range
of 2.4−3.5 in the pH range of 7−9, whereas an unusual K2/K1
ratio of 11.2 was observed at pH 6. We ascribed this to the
shallowly perching bis-quinoline chromophores on the rim of
CDx, which reduced the coinclusion of quinoline with AC but
promoted the complexation of the AC pair,9,10,12,14 and the
reduced electrostatic interaction between carboxylates at acidic
pH. Indeed, the calculated populations suggested that the 1:2
complexes of AC and 7 were apparently improved at lower pH
(see Table S4 in the Supporting Information).
Photolyses of AC in the absence and presence of CDx
derivatives were performed in an aqueous PBS buffer at
different pH values, using a 365-nm light-emitted diode (LED)
lamp. The chemical yields, product ratios (HH/HT and anti/
syn), and enantiomeric excess (ee) values of the photoproducts
Supporting Information.11 It turned out that photolyses at
lower pH significantly improved the yields of HH cyclodimers
of 3 (up to 52.3%) and 4 (up to 34.0%), regardless of the host
employed (Table 2), demonstrating that the pH plays a
significant role in the photoreaction.
The enantioselectivity also showed a critical dependence on
the pH. In particular, the bis-quinoline-tethered host 7 gave 3
in 25.2% ee and −64.4% ee at pH 1 and 6, respectively.
Whereas, the ee of HT cyclodimer 2 was decreased
considerably for all hosts 5−7 in the acidic pH range.
Interestingly, the use of N-methylated bis-quinoline tethered
host 8 resulted in a significant chirality inversion in the range
of 41.2% to −76.2% ee for HH cylodimer 3 upon changing the
pH of the solution from acidic to basic (see Table 2, as well as
Table S9). These results implied that, in the acidic pH range,
the carboxylic acid group of AC destabilized the HT
orientation and enhanced the HH orientation in the cavity
of hosts.
Figure 1. Structure of supramolecular hosts 5−8.
Monosubstituted γ-CDx derivatives 6, 7, and 8 were
synthesized by selective tosylation of native γ-CDx, followed
by sequential amination and substitution reactions (see
the Supporting Information).11 The absorption spectra of host
7 showed the absorption peaks at 226, 284, and 315 nm, which
are assignable to the 1Bb, 1La, and 1Lb transitions of the
quinoline chromophore (see Figure S14 in the Supporting
Information). The conformational properties of the tethered
bis-quinoline chromophore in 7 were analyzed by circular
dichroism (CD) spectroscopic studies.12,13 Interestingly, host
7 in water and methanol showed very different CD signal(s)
(see Figure S15 in the Supporting Information),11 giving
strong negative exciton coupling-type CD spectrum in water,
but almost no CD response in methanol. This indicated the
different orientations of the quinoline chromophore in the two
solvents.13,11 According to the “sector rule”,12 the observed CD
signals of 7 in water indicated that the anchored quinoline
chromophores was located inside their CDx cavities,13,11 while
it could move into or out of the CDx cavity in methanol
(MeOH) to cancel the CD response, because of a lack of
strong hydrophobic interaction. Decreasing the pH to 2−4
considerably reduced the CD response of 7 (see Figure S16 in
the Supporting Information), demonstrating that the location
of quinoline chromophore became shallow upon protonation
of the quinolines (pKa7 = 4.49; see Table S10 in the
Supporting Information).11
To understand the pH-dependent behavior, the acid
dissociation constant (pKa) of AC in the absence and presence
of a host was investigated by ultraviolet−visible light (UV-vis)
and fluorescence spectral changes at various pH (Figures S26−
S29 in the Supporting Information). With the pH of the
solution containing AC and a CDx derivative lowered from
pH-dependent complexation of hosts 6 and 7 with AC was
studied by comparing to the complexation of native γ-CD with
AC (K1 = 161 25 M−1; K2 = 38 500 3300 M−1),9b K1
values of host 7 were generally improved while K2 were
decreased (Table 1), indicating that the tethered bis-quinoline
chromophore in 7 greatly facilitated the first binding of AC
molecules to the cavity, presumably because of the coinclusion
of one quinoline in the cavity. The relatively strong binding
constants ensured that the ACs included are not able to release
1
basic (9 or 10) to acidic (2 or 1), the La band of AC was
gradually bathochromic-shifted, showing an isosbestic point at
399 nm (for 6) or 396 nm (for 7). The pKa values were
improved from 4.35 for AC in the absence of any host
molecule15 to 5.8, 5.28, and 4.93 in the presence of 0.2 mM of
5, 6, and 7, respectively (Table S10 in the Supporting
Information).11 The determined values were apparently higher
B
Org. Lett. XXXX, XXX, XXX−XXX