Synthesis, characterization, and small hydrocarbon encapsulation of dicavitand-porphyrins

Article abstract of DOI:10.1246/bcsj.20120107

New host molecules "Dicavitand-Porphyrins" [H₂C ₂P(syn,syn) (3), H₂C₂P(syn,anti) (4)] with small cavities on one or both sides of the porphyrin plane were synthesized from 5,10-bis(2,6-dihydroxyphenyl)-15,20-dip

Full text of DOI:10.1246/bcsj.20120107

912
Bull. Chem. Soc. Jpn. Vol. 85, No. 8, 912-919 (2012)
© 2012 The Chemical Society of Japan
Synthesis, Characterization, and Small Hydrocarbon
Encapsulation of Dicavitand-Porphyrins
Jun Nakazawa,*1 Jun Hagiwara,2 Yuichi Shimazaki,3 Fumito Tani,2 and Yoshinori Naruta*2
1Department of Material and Life Chemistry, Faculty of Engineering, Kanagawa University,
3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama, Kanagawa 221-8686
2Institute for Materials Chemistry and Engineering, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581
3Department of Science, College of Science, Ibaraki University, 2-1-1 Bunkyo, Mito, Ibaraki 310-8512
Received April 5, 2012; E-mail: jnaka@kanagawa-u.ac.jp
New host molecules “Dicavitand-Porphyrins” [H2C2P(syn,syn) (3), H2C2P(syn,anti) (4)] with small cavities on one
or both sides of the porphyrin plane were synthesized from 5,10-bis(2,6-dihydroxyphenyl)-15,20-diphenylporphyrin
and bis(chloromethyl)cavitand in 15 and 34% yield, respectively. Similarity of guest size selectivity of the host 4 in
comparison with the reported “Cavitand-porphyrin” [H2CP(syn) (1)] suggests that these hosts have the same cavity size.
1
The 1:1 and 1:2 association constants (K11 and K12) of the guest encapsulations into 3 were also obtained by H NMR
titration and nonlinear least square fittings. The guest size dependences of K11 and K12 values of 3 show that the initial
cavity prefers larger guests such as ethane, while the second one does not. The induced-fit type very small structural
changes (estimated within 1 ¡) upon first guest encapsulation of the host 3 affects the guest encapsulation of the other
cavity through the covalent linkages.
The encapsulation of small molecules is an important
in Figure 1) which has a small cavity at one side of the
porphyrin plane and had investigated encapsulation of small
molecules into this capsule cavitiy.58-61 The cavity shows high
affinity for small hydrocarbons such as methane and ethane.
In addition, we also reported induced-fit-type structural change
of the capsule upon the guest encapsulation. We considered that
the very small structural change (estimated within 1 ¡) of the
host can be used as a stimulus to multiguests encapsulation.
Similar strategy is known in biological systems such as the
allosteric effect of oxygen binding of hemoglobin by protein
structural change.62,63
In this article, we aimed to change affinity for a second guest
by a host structural change upon first guest encapsulation.
We synthesized new host molecules H2C2Ps having two
cavitands and a porphyrin similar to reported H2CPs 1 and 2.
This H2C2Ps are considered to have three structural isomers
(syn,syn; 3), (syn,anti; 4), and (anti,anti; 5) with respect to
orientation of the two cavitand groups, as shown in Figure 1.
The (syn,syn) isomer 3, of H2C2Ps has a cavity on either sides
of the porphyrin plane, and both cavitands were connected by
two 2,6-dihydroxyphenyl groups at 5,15-meso-position of the
porphyrin. We expected that a structural change of the cavities
through these linkers upon encapsulation of the first guest
would alter the selectivity for second guest encapsulation.
research area of molecular recognition chemistry for applica-
tions such as gas storage, sensors, and chemoselective reactions
within the host cavities, as well as the basic study of weak
intermolecular interactions.1-7 In terms of small molecules,
hydrocarbons are one of the most difficult guests to target
for recognition, as they lack functionalities that form strong
interactions with host molecules. To encapsulate small hydro-
carbon molecules reversibly, it is necessary to prepare cavities
that have suitable pore sizes for guests and flexible gate
system.8-26 The size relation between host cavity and guests
has been studied by many researchers especially by Rebek
and co-workers.27 To improve the versatility and applicability
of encapsulation systems, an additional substituent group or a
triggering event in the host system is needed to be built in.3,28-38
Multiple guest encapsulations in one host molecule is one of the
methods, and has many potential benefits: (1) Increased guest
capacity for molecular storage applications.39-41 For example,
Atwood and co-workers reported that multiple small molecule
storage in resorcin[4]arene crystals.42,43 (2) Selective reactivity
between encapsulated guests in host cavities termed molecular
reaction flasks.4,44,45 (3) Guest selectivity control upon addition
of external stimuli for “smart” sensor applications.46 Rebek and
co-workers reported a coencapsulation method that changed the
selectivity for the second guest within the large cavity of the
cylindrical molecular capsule by decreasing the cavity volume
though addition of the first guest.47-53 In addition, the guest
selectivity change via the cavity size control using addition of
spacers has been reported.54-57
Results and Discussion
Synthesis of H2C2Ps. As the precursor of the cavitand
moiety of H2C2P, bis(chloromethyl)cavitand 6 was synthe-
sized based on a previous report.59 To prepare the porphyrin
part, a mixture of meso-bis(2,6-dimethoxyphenyl)diphenyl-
porphyrin (7) was synthesized from mixed condensation of
In our previous studies, we had synthesized capsule-like
hosts “Cavitand-Porphyrin” H2CP(syn) (1, structure is shown
Published on the web August 3, 2012; doi:10.1246/bcsj.20120107

J. Nakazawa et al.
Bull. Chem. Soc. Jpn. Vol. 85, No. 8 (2012)
913
Figure 1. Structures of H2CPs 1 and 2 and H2C2Ps 3, 4, and 5.
OMe
CHO
H
N
2,6-dimethoxybenzaldehyde, benzaldehyde, and pyrrole with
Montmorillonite K10 as a heterogeneous acid catalyst, and
subsequent in situ oxidation by 2,3-dichloro-5,6-dicyano-1,4-
benzoquinone (DDQ) in 19% yield.64 Since the separation of
the 5,10- and 5,15-disubstituted porphyrin isomers is difficult
by silica gel column chromatography, the mixture was directly
used in the next step. The methyl groups in compound 7 were
removed by pyridine hydrochloride at 210 °C. 5,10-Bis(2,6-
dimethoxyphenyl)-15,20-diphenylporphyrin (8) was obtained
in 46% yield by silica gel column chromatography to remove
5,15-isomer and their decomposed by-products.
+
+
CHO
a)
OMe
MeO
OMe
N
H
N
H
MeO
OMe
+
N
N
N
N
H
H
MeO
MeO
N
N
OMe
b)
OMe
7 (mixture)
Synthesis of H2C2Ps were carried out by similar procedure
of reported H2CPs, 1 and 2 (Figure 2).59 TLC analysis (silica
gel, benzene) of crude product showed two new low-polarity
reddish-purple spots (more polar spot; 4, the other spot; 3).
These products were separated by silica gel column chro-
matography. Since HR-MS spectra and elemental analyses of
compound 3 and 4 show good correlations with the dicavitand-
porphyrin formula, we determined that 3 and 4 were structural
isomers of H2C2Ps. To distinguish structure of isomers 3 and 4,
we obtained these 1D-1H and 1H-1H COSY NMR spectra. The
1H NMR spectra of 3 shows a more symmetric pattern than that
of 4 and similar to that of H2CP(syn) (1). On the other hand,
the 1H NMR signal pattern of 4 correlates to a 1:1 mixture of 1
and 2. Thus compound 3 was characterized as H2C2P(syn,syn)
that has two cavitands covering the porphyrin, and compound
4 was characterized as H2C2P(syn,anti) that has only one
cavitand covering the porphyrin, respectively. The polarity of
H2C2Ps in TLC analysis (4 is polar than 3) also supports this
R =
OH
O
O
N
O
O
O
HO
HO
H
R
R
R
N
N
H
R
N
Cl
O
OH
8
O
O
6
Cl
c)
+
4
+
3
5
~0%
Yield: 15% 34%
Figure 2. Synthesis of H2C2Ps. a) (1) Montmorillonite
K10, CH2Cl2, RT, overnight. (2) DDQ, CH2Cl2, RT, 1 h,
19%. b) Py¢HCl, 210 °C, 2 h, 47%. c) K2CO3, THF/NMP,
120 °C, 4 d.

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Bull. Chem. Soc. Jpn. Vol. 85, No. 8 (2012)
Guest Binding of Dicavitand-Porphyrins
Table 1. 1H NMR Chemical Shifts (ppm) of Encapsulated
Hydrocarbons into 1, 3, and 4 in CDCl3 at 25 °C
Guest
Free
1a)
3 (1:1) 3 (1:2)
4
g)
Methane
Acetylene
Ethylene
Ethane
Cyclopropane
n-Propane
0.15
1.91
5.39
0.85
0.23
¹7.19 ¹7.37 ¹7.36 ¹7.22
¹5.37 ¹5.80 ¹5.72 ¹5.47
¹2.07 ¹2.31 ¹2.24 ¹2.13
¹6.49 ¹6.72 ¹6.65 ¹6.57
¹6.95 ¹7.21 ¹7.11 ¹7.05
*
*
f)
@
*
e)
d)
c)
b)
b)
b)
b)
b)
1.31, 0.88
®
®
®
®
@
*
a) From Ref. 59. b) Not encapsulated.
@
*
R
R
R
R
R
R
R
R
@
*
O
O
O
O
O
O
O
O
O
O
O
O
O
O
H
O
O
O
H
Hi
HN
@
O
*
O
Ph
Hi
Ph
Ph
O
N
NH
HN
N
N
N
H
a)
N
Ph
O
O
4
1
10
8
6
4
2
0
–2 –4 –6 –8
Hi'
H
O
O
O
O
O
Chemical shift / ppm
O
O
Figure 3. 1H NMR spectra of small hydrocarbons encapsu-
lation into 4 in CDCl3 at 25 °C. a) Free 4, b) methane,
c) acetylene, d) ethylene, e) ethane, f) cyclopropane,
g) n-propane. @: encapsulated guest signals, *: free guest
signals.
CH4
O
NH
R
R
R
R
Hi (CH4@1)
Hi (1)
b)
characterization according to the H2CP case. The syn isomer
1 of H2CP shows less polarity than the anti isomer 2 in TLC
analysis (silica gel, benzene), because of the -O-CH2-O-
groups at the rim of the cavitand in syn form are covered
by the porphyrin plane to prevent interaction with the silica
gel surface. It is worth mentioning that the isomer 5 is not
formed under current reaction condition. The yields of isomers
[3 (15%), 4 (34%), and 5 (0%)] may correlate to degree of
structural strain around the hinges of the intermediates in the
transition state of the irreversible ring closure process, and the
“strainless” (syn,anti) transition intermediate may convert to
the strainless product 4. In addition, the yields also show that
structural orientation of one cavitand affects to the cavitand
on the other side through restricted rotation of the two meso-
phenyl linkers of the porphyrin connecting the two cavitands. It
is easy to imagine that the structural effect causes difference in
guest encapsulation affinity between the two cavities of 3.
Encapsulation of Small Hydrocarbons into the Host 4.
The H2C2P(syn,anti) (4) has a cavity suitable for small guest
encapsulation at one side (syn side) of the porphyrin. The
encapsulations of small hydrocarbon guests into the cavity of
NH
–3
Hi (CH4@4)
Hi (4)
Hi' (CH4@4)
Hi' (4)
a)
0
–1
–2
Chemical shift / ppm
Figure 4. The Hi signal shifts of a) 4 and b) 1 upon methane
1
encapsulation in H NMR in CDCl3 at 25 °C.
larger than that of methane/1 system (¦¤ = ¹7.34 ppm). This
shift seen in 4 is caused by additional shielding from the
cavitand on the other side of the porphyrin plane. In our earlier
work, we reported that the Hi signal in host 1 shifts downfield
upon encapsulation of methane, due to structural change of
the cavity. In the case of 4, Hi signal also shifts downfield. In
addition, we can see that Hi¤ signal of 4 (the proton located on
the anti side cavitand) shifts downfield (Figure 4). Hi¤ shows
that a structural change in the syn side cavity upon encapsu-
lation of methane affects the structure of the anti side cavitand
through the two covalent linkers connecting the two cavitands.
New signals appeared at the extremely high field region
upon addition of small hydrocarbons such as acetylene, ethyl-
ene, ethane, and cyclopropane by bubbling into the CDCl3
solution of 4. In contrast, addition of larger hydrocarbons than
the above guests, such as propane does not show any new
signals except for the free propane signals. Thus the cavity of
4 can encapsulate small hydrocarbons from methane up to
cyclopropane, size selectively. Since the host 1 can also encap-
1
4 were observed by H NMR in CDCl3 at 25 °C, as shown
in Figure 3. Upon bubbling of methane gas into the 5 mM
solution of 4, a new signal appeared at ¹7.22 ppm in addition
to a free methane signal at 0.15 ppm (Figures 3a to 3b). We
characterized the new signal of the methane/4 system as the
encapsulated methane in the syn side cavity. This signal
correlates with the reported methane/1 system which shows
an encapsulated methane signal at ¹7.15 ppm under the same
condition (Table 1).59 The signal shift magnitude (¦¤ = ¹7.37
ppm) between free and encapsulated methane in 4 is slightly

J. Nakazawa et al.
Bull. Chem. Soc. Jpn. Vol. 85, No. 8 (2012)
915
sulate small hydrocarbons up to cyclopropane, host 1 and 4
have almost the same size cavity.
of the porphyrin plane, we characterized the first new signal
at ¹7.37 ppm and the second signal at ¹7.36 ppm as encapsu-
lated methane protons of the 1:1 and 1:2 association modes,
respectively (Table 1). Due to the structure of 1:2 association
mode has mirror plane symmetry with respect to the porphyrin
plane within the NMR time scale, the signals of two encap-
sulated methane molecules in cavitands on either side appeared
at the same chemical shift ¹7.36 ppm. In addition, the 1:2
signal appearing downfield of the 1:1 signal may be caused
by decreasing shielding of the cavitand and the porphyrin by
enlarging both cavities upon the second guest encapsulation.
Since methane is the smallest guest we used, the shift magnitude
of encapsulated methane signals between 1:1 and 1:2 modes
of the methane/3 system is small compared to other guests.
The encapsulation of other small hydrocarbons into 3 was
also monitored by 1H NMR titration. The cavities of 3 can
encapsulate small hydrocarbon guests from methane to cyclo-
propane in similar fashion to hosts 1 and 4, as determined by
To obtain further information on guest selectivity of host 4,
we carried out guest titrations and calculated 1:1 association
constants K11 of 4 using eq 1. The K11 values of small hydro-
carbon guests/4 system and the plot for the methane/4 system
are shown in Table 2 and Figure S1, respectively. The isomer
4 has similar K11 values and trend for guest selectivity (that
is high affinities for methane and acetylene) to isomer 1,
suggesting that 1 and 4 have similar size cavities. This cavity
size similarity also shows that the additional cavitand at the
anti side of the host 4 makes no steric distortion of the syn
side cavity through two linkers that connect the syn and anti
cavitands.
Encapsulation of Small Hydrocarbons into 3. Encapsu-
lation of small hydrocarbon molecules into host 3 was
monitored by 1H NMR titrations. Change in 1H NMR spectrum
upon addition of methane into 2 mM CDCl3 solution of 3 is
shown in Figure 5. A new signal appears at ¹7.37 ppm that
initially increases in intensity with addition of small amount of
methane. Upon further addition of methane, this signal starts
decreasing in intensity while another new signal that continues
to increase appears on the shoulder of the first signal at
¹7.36 ppm. Since the host 3 has two small cavities at both sides
1
the appearance of a new H NMR signal at extreme high field
(Table 1). The spectral change upon addition of ethane into a
CDCl3 solution of 3 is shown in Figure 6 as an example, and
spectral changes upon addition of acetylene, ethylene, cyclo-
propane, and propane are shown in Figures S2-S5 in the
Supporting Information. Upon the addition of a small amount
of ethane gas into a CDCl3 solution of 3 (2 mM), a new signal
appeared at ¹6.72 ppm in the 1H NMR spectrum. By increasing
concentration of ethane, the signal intensity changes, increasing
at first and then decreasing. The decrease of the signal at
¹6.72 ppm corresponds with the appearance of a new signal
at ¹6.65 ppm. We ascribe the pattern of 1H NMR signals to the
encapsulation of ethane in 3 in a 1:1 and 1:2 ratio. In methane/
3 system, the chemical shift difference between the encapsu-
lated methane signals of 1:1 and 1:2 modes is very small (¦¤ =
0.01 ppm), and a host signal at 6.3 ppm shows no change. In
contrast, the shift difference of encapsulated ethane is large
(¦¤ = 0.07 ppm), and the host signal at 6.3 ppm also shifts
Table 2. The 1:1 and 1:2 Association Constants (K11 and
K12, M¹1) of Hydrocarbons Encapsulation into 1, 3, and 4
1
in CDCl3 at 25 °C Obtained by H NMR Titrations
Guest
1 (K11)a)
3 (K11)
3 (K12)
4 (K11)
Methane
81 « 18 257 « 21 136 « 12 108 « 5
130 « 20 707 « 40 201 « 12 141 « 5
Acetylene
Ethylene
Ethane
49 « 5
9 « 1
281 « 20 182 « 14
55 « 3
9 « 1
4 « 1
135 « 9
179 « 5
16 « 1
11 « 1
Cyclopropane
10 « 2
a) From Ref. 59.
CH4free
CH4in
CHCl3
b)
a)
1:2
c)
3
+
CH4
1:1
3
10
8
6
4
2
0
–2
–4
–6
–8
6.6
6.4
6.2
–7.3
–7.4
Chemical shift / ppm
Figure 5. 1H NMR spectral changes of 3 upon addition of methane in CDCl3 at 25 °C. a) Full spectra, b) selected expanded view of
host signals (6.2-6.6 ppm), and c) expanded view of the signals of encapsulated methane.

916
Bull. Chem. Soc. Jpn. Vol. 85, No. 8 (2012)
Guest Binding of Dicavitand-Porphyrins
a)
b)
c)
C2H6in
CHCl3 C2H6
1:2
3
1:2
1:2
+
C2H6
1:1
1:1
free
3
10
8
6
4
2
0
–2 –4 –6 –8
6.6
6.4
6.2
–6.6
–6.8
Chemical shift / ppm
Figure 6. 1H NMR spectral changes of 3 upon addition of ethane in CDCl3 at 25 °C. a) Full spectra, b) selected expanded view of
host signals (6.2-6.6 ppm), and c) expanded view of the signals of encapsulated ethane.
upon the ethane encapsulation. The significant spectral change
caused by structural reorganization upon ethane encapsulation
is a result of the larger size of this guest in comparison to
methane. The chemical shift difference between 1:1 and 1:2
modes (Table 1) and host signal changes (Supporting Informa-
tion Figures S2-S5) correlate with guest size, with acetylene
being the exception. The acetylene/3 system shows a different
trend; a large chemical shift difference of the 1:1 and 1:2
encapsulated acetylene signals, and in addition, a significant
chemical shift change of N-H proton signals of the host
porphyrin. The specific difference may caused by the acidic
character of acetylene C-H.65
guest encapsulation of host 3 shows higher affinities for bigger
guests by the comparison of the K11 values. The guest affinity
trend for 3 depends on guest hydrocarbon size and is relatively
similar to that of a hydrogen bonding type CA-PyP host60
which has a larger cavity than 1 (K11 for methane = 56,
acetylene = 202, ethylene = 690, ethane = 527, and n-pro-
pane = 236 M¹1). The high affinity for larger guest supposes
that the range of motion of the hinges connecting the porphyrin
and the cavitands in host 3 are different to that of host 1.
Generally, initial and second binding events of a host having
two “independent” sites follow statistics in a K12/K11 ratio of
0.25.66 The K12/K11 ratios for encapsulations of smaller guests
such as methane (0.53), acetylene (0.28) and ethylene (0.64)
into the host 3 are larger than 0.25 indicating that the cavities of
the host show positive cooperativity for these smaller guests.
Upon increasing of guest size up to ethane (K12/K11 = 0.11)
and cyclopropane (0.06), the cooperativity between the cavities
of the host 3 turns to the opposite negative direction. The
van der Waals interaction between such larger initial guest and
the porphyrin plane tilts the porphyrin toward the second free
cavity side. This affinity change can be categorized to a kind of
allosteric effect via induced-fit type host structural change with
weak van der Waals interaction between a host and guests.
1
The H NMR spectral differences between the 1:1 and 1:2
association modes of guest/3 systems can be attributed to a
host structural change upon encapsulation of the first guest. We
expected that this host structural change upon encapsulation of
the first guest would influence the second association process.
To check the guest association affinity of 3, we carried out
1
titrations of intensity change of the guest H NMR signal at
different guest concentrations. The 1:1 and 1:2 association
constants for various guests with the host 3 were obtained by
nonlinear least square fitting using eq 7 (Figure S6). Due to
overlap of the 1:1 and 1:2 encapsulated methane signals, we
used the sum concentration [G]in of the 1:1 and 1:2 encapsu-
lated guests for the calculation. In the methane/3 system, the
titration was hampered before full encapsulation by the low
solubility of methane in CDCl3. Generally, these limitations
decrease accuracy of K12 values. In addition, we could not
titrate to the endpoint (full encapsulation) due to the low
affinity of 3 for these guests in ethane/3 and cyclopropane/3
systems. The calculated values of K11 and K12 are shown in
Table 2. In contrast to hosts 1 and 4 those have high affinities
for smaller guests such as methane and acetylene, the initial
Conclusion
We have synthesized and studied encapsulation event of a
series of host molecules (H2C2Ps) with cavitands on either side
of a porphyrin molecule, connected via the same meso-aromatic
ring of the porphyrin. It was expected that the synthesis of
H2C2Ps would afford three structural isomers 3(syn,syn),
4(syn,anti), and 5(anti,anti) due to a difference in cavitand
direction. However, host 4 was generated in high yield than 3,
and compound 5 was not generated under our conditions.

J. Nakazawa et al.
Bull. Chem. Soc. Jpn. Vol. 85, No. 8 (2012)
917
We evaluated small hydrocarbon encapsulation into 4, which
has a cavity on the syn side of the porphyrin plane, with a
reported similar host H2CP(syn) (1). The host 4 exhibits the
same trend of guest encapsulation properties as compared to 1,
demonstrating that the cavity structure on the syn side of 4 is
very similar to 1, because the anti-cavitand does not influence
this binding process. In addition, we observed the NMR signal
shifts of the Hi¤ proton of anti-cavitand caused by a structural
change of guest encapsulation at syn side cavity through the
two linkers.
give 7 as a purple solid in 19% yield (0.16 g, 0.24 mmol). The
product was dried in vacuo at room temperature for 3 h prior to
the next reaction.
1
7: H NMR (CDCl3): ¤ 8.76 (m, 8H, pyrrole-¢), 8.21 (d,
J = 7.6 Hz, 4H, Ph-4), 7.73 (m, 8H, Ph-2,3,5,6 + (OH)2Ph-4),
7.01 (d, J = 8.4 Hz, 4H, (OH)2Ph-3,5), 3.52 + 3.51 (s + s,
12H, Me), ¹2.61 + ¹2.62 (s + s, 2H, NH). HR-MS
(C48H38N4O4): m/z = calcd 734.2893, found 734.2888.
Synthesis of 5,10-Bis(2,6-dihydroxyphenyl)-15,20-di-
phenylporphyrin (8). The methoxy-substituted porphyrin 7
(120 mg, 160 ¯mol) was heated in excess pyridine hydrochlo-
ride for 2 h at 210 °C under N2 atmosphere. After the mixture
was cooled below 100 °C, the reaction mixture was treated with
water. The residue was extracted with AcOEt, and the organic
layer was washed with 0.1 M HCl, saturated solution of
NaHCO3 in water, and brine. The organic layer was dried with
Na2SO4, and then the solvent was evaporated under reduced
pressure. The residue was purified by silica gel column
chromatography (CH2Cl2/AcOEt = 95/5-92/8, the second
fraction band) to give 8 as a reddish purple solid in 46% yield
(50 mg, 73.7 ¯mol). The product was dried in vacuo at 120 °C
for 3 h prior to the next reaction.
Small hydrocarbon encapsulation into host 3, which has
cavities on either side of the porphyrin plane, was monitored
by 1H NMR titrations. We observed signals of free host, as well
1
as the 1:1 and 1:2 association states separately by H NMR
spectra. The difference of encapsulated guest chemical shifts
between 1:1 and 1:2 associations becomes larger with increas-
ing guest size. This can be rationalized by the changing of
magnetic shielding effect caused by induced-fit-type structural
change of the host. This structural change accounts for the
difference of guest encapsulation affinity of the free and 1:1
associated host 3. The guest size dependences of K11 and K12
values of 3 show that the initial cavity prefers larger guests
such as ethane, while the second one does not.
1
8: H NMR (CDCl3): ¤ 8.99 (s, 2H, pyrrole-¢), 8.94 (s, 4H,
There are many reports that demonstrate an allosteric effect
due to host structural changes using hydrogen or coordination
bonds. In contrast, our system shows an allosteric effect via
induced-fit-type host structural change with weak van der
Waals interaction between a host and guests.
pyrrole-¢), 8.88 (s, 2H, pyrrole-¢), 8.21 (d, J = 6.3 Hz, 4H,
Ph-4), 7.80 (m, 6H, Ph-2,3,5,6), 7.61 (t, J = 8.3 Hz, 2H,
(OH)2Ph-4), 6.97 (d, J = 8.3 Hz, 4H, (OH)2Ph-3,5), 4.69 (br,
4H, OH), ¹2.71 (s, 2H, NH). HR-MS (C44H30N4O4): m/z =
calcd 678.2267, found 678.2238.
Synthesis of H2C2Ps (syn,syn-Isomer 3, syn,anti-Isomer 4,
and anti,anti-Isomer 5). ATHF/NMP (1:1, 100 mL) solution
of cavitand 6 (550 mg, 520 ¯mol), porphyrin 8 (160 mg,
236 ¯mol), and K2CO3 (1.0 g) were heated in an autoclave at
120 °C for 4 days. The mixture was evaporated to remove
THF. 200 mL of CH2Cl2 was added to the mixture, and the
organic layer was washed with 1 M HCl and water, and then the
solvent was evaporated under reduced pressure. The residue
was purified by silica gel column chromatography (benzene).
Isomers 3 and 4 of H2C2Ps were obtained as the first and
second porphyrin fractions in 15 and 34% yield, respectively.
The isomer 5 was not obtained.
Experimental
Materials and Instruments.
Commercially available
reagents and solvents were used without further purification
unless otherwise noted. Tetrahydrofuran (THF) was dried
over KOH, and distilled from sodium diphenylketyl under
N2 atmosphere. N-Methylpyrrolidone (NMP) was dried over
molecular sieves 4A for several days. CDCl3 (99.8 atom % D,
ACROS ORGANICS) was passed through an alumina column.
Cavitand-Porphyrins (syn; 1), (anti; 2), and bis(chloromethyl)-
cavitand 6 were synthesized according to literature.59
1H NMR spectra were recorded on a JEOL JMX-GX400
(400 MHz) spectrometer. 1H NMR chemical shifts (¤) are
reported in parts per million (ppm) relative to TMS using the
residual proton resonance of CDCl3 (¤ = 7.26 ppm). High-
resolution MS (HR-MS) spectra were recorded on a JEOL
LMS-HX-110 spectrometer. FAB-MS spectra were measured
with 3-nitrobenzyl alcohol as matrix.
Synthesis of meso-Bis(2,6-dimethoxyphenyl)-meso-Di-
phenylporphyrin (mixture of 5,10- and 5,15-isomers, 7).
To a suspension of Montmorillonite K10 (10 g), 2,6-dimethoxy-
benzaldehyde (0.42 g, 2.5 mmol), and benzaldehyde (0.27 g,
2.5 mmol) in 100 mL of CH2Cl2, pyrrole (0.35 mL, 5.1 mmol)
were added at RT under N2 atmosphere. The reaction mixture
was stirred for overnight and then DDQ (0.85 g, 3.7 mmol)
were added. After stirring of the mixture for additional hour,
Montmorillonite K10 was removed from the mixture by filtra-
tion and well washed with CH2Cl2. The filtrate was passed
through an alumina column, and then the solvent was evapo-
rated under reduced pressure. The residue was purified by silica
gel column chromatography (benzene, third fraction band) to
1
3: H NMR (500 MHz, CDCl3): ¤ 9.17 (br, 2H, pyrrole-¢),
9.10 (br, 2H, pyrrole-¢), 8.98 (br, 2H, pyrrole-¢), 8.64 (d, J =
6.9 Hz, 4H, Ar-H of porphyrin), 8.33 (br, 2H, pyrrole-¢), 7.91-
7.83 (m, 10H, Ar-H of porphyrin), 7.23 (d, J = 8.7 Hz, 2H,
Ar-H of porphyrin), 7.15-7.05 (m, 24H, CHCH2H2Ph), 6.95-
6.85 (m, 16H, CHCH2H2Ph), 6.48 (s, 4H, Ar-H of cavitand),
6.30 (s, 4H, Ar-H of cavitand), 5.33 (d, J = 7.6 Hz, 2H, Hco of
-OCH2O-), 5.13 (d, J = 7.3 Hz, 4H, Hbo of -OCH2O-), 4.94
(d, J = 8.6 Hz, 4H, -OCH2Ar- of linker), 4.86 (s, 4H, Ar-H
of cavitand), 4.72 (d, J = 8.6 Hz, -OCH2Ar- of linker), 4.35-
4.20 (m, 6H, CHCH2CH2Ph), 4.10 (br, 2H, Hao of -OCH2O-),
3.99 (t, J = 7.8 Hz, 2H, CHCH2CH2Ph), 2.40-2.10 (m, 18H,
CHCH2CH2Ph + Hci), 2.10-1.90 (m, 16H, CHCH2CH2Ph),
1.81 (br, 4H, Hbi of -OCH2O-), ¹0.05 (br, 2H, Hai of
-OCH2O-) ¹3.41(s, 2H, NH). HR-MS (C176H142N4O20):
m/z = calcd 2631.0217, found 2631.0205. Elemental analysis
(after reprecipitation from methanol): calcd for C176H142N4O20¢
2MeOH: C, 79.27; H, 5.61; N, 2.08%. Found: C, 79.17; H,
5.43; N, 2.37%.

918
Bull. Chem. Soc. Jpn. Vol. 85, No. 8 (2012)
Guest Binding of Dicavitand-Porphyrins
1
4: H NMR (500 MHz, CDCl3): ¤ 9.12 (br, 2H, pyrrole-¢),
8.95 (br, 2H, pyrrole-¢), 8.87 (s, 2H, Ar-H of porphyrin), 8.55
(br, 2H, pyrrole-¢), 8.44 (s, 2H, Ar-H of porphyrin), 8.34 (br,
2H, pyrrole-¢), 7.86 (t, J = 8.4 Hz, 2H, Ar-H of porphyrin),
7.80 (br, 4H, Ar-H of porphyrin), 7.41 (d, J = 8.4 Hz, 2H,
Ar-H of porphyrin), 7.14 (d, J = 8.4 Hz, 2H, Ar-H of
porphyrin), 7.13-7.01 (m, 24H, CHCH2H2Ph), 6.94-6.86 (m,
16H, CHCH2H2Ph), 6.84 (s, 2H, Ar-H of cavitand), 6.70 (br,
2H, Ar-H of porphyrin), 6.54 (s, 2H, Ar-H of cavitand), 6.53
(s, 2H, Ar-H of cavitand), 6.51 (s, 2H, Ar-H of cavitand), 6.48
(s, 2H, Ar-H of cavitand), 6.28 (s, 2H, Ar-H of cavitand), 5.97
(d, J = 6.9 Hz, 2H, Hbo of -OCH2O- (anti)), 5.73 (d, 2H,
J = 7.2 Hz, Hbo of -OCH2O- (syn)), 5.72 (br, 1H, Hao of
-OCH2O- (anti)), 5.25 (br, 1H, Hco of -OCH2O- (syn)), 5.12
(d, J = 8.0 Hz, 2H, -OCH2Ar- of linker (syn)), 4.95 (d, J =
8.0 Hz, -OCH2Ar- of linker (syn)), 4.71 (t, 1H, J = 8.0 Hz,
CHCH2CH2Ph (anti)), 4.64 (t, 2H, J = 8.0 Hz, CHCH2CH2Ph
(anti)), 4.49 (d, 2H, J = 7.2 Hz, Hbi of -OCH2O- (syn)),
4.45-4.40 (m, 3H, Hbi of -OCH2O- (anti) + CHCH2CH2Ph
(anti)), 4.31 (br, 2H, CHCH2CH2Ph (syn)), 3.94 (br, 1H,
CHCH2CH2Ph (syn)), 3.91 (d, J = 8.3 Hz, 2H, -OCH2Ar-
of linker (anti)), 3.57 (d, J = 8.1 Hz, 2H, -OCH2Ar- of
linker (anti)), 3.21 (br, 1H, Hao of -OCH2O- (syn)), 2.95 (t,
J = 8.0 Hz, 1H, CHCH2CH2Ph (syn)), 2.84 (br, 1H, Hai of
-OCH2O- (anti)), 2.59-1.50 (m, 33H, CHCH2CH2Ph + Hci
(syn)), 1.03 (br, 1H, Hco of -OCH2O- (anti)), ¹0.66 (br,
2H, Hai of -OCH2O- (syn)) ¹1.70 (br, 1H, Hci of -OCH2O-
(anti)), ¹2.93 (s, 2H, NH). HR-MS (C176H142N4O20):
m/z = calcd 2631.0217, found 2631.0173. Elemental analysis
(after reprecipitation from methanol): calcd for C176H142N4O20¢
MeOH: C, 79.77; H, 5.52; N, 2.10%. Found: C, 79.71; H, 5.62;
N, 2.08%.
½Gꢀin ¼ ½H¢Gꢀ þ 2½H¢G2ꢀ
2
¼ fK11½Gꢀ þ 2K11K12½Gꢀ g½Hꢀ
ð6Þ
ð7Þ
2
K11½Gꢀ þ 2K11K12½Gꢀ
½Gꢀin
¼
½Hꢀo
2
1 þ K11½Gꢀ þ K11K12½Gꢀ
This work was supported by the Grants-in-Aid for Scientific
Research on Priority Areas (No. 15036254) from MEXT and
Scientific Research (A)/(S) (Nos. 14204073 and 17105003)
and for Exploratory Research (No. 16655039) from JSPS as
well as by a grant from The Asahi Glass Foundation. J. N.
acknowledges JSPS Research Fellowship.
Supporting Information
The plots and curve fittings for determination of association
constants (Figures S1 and S6). H NMR spectral changes upon
1
encapsulation of acetylene, ethylene, cyclopropane, and pro-
pane into 3 (Figures S2-S5). Assignments of 1H-1H COSY
spectra of host 3 and 4 (Figures S7 and S8). This material
is available free of charge on the web at: http://www.csj.jp/
journals/bcsj/.
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¼
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