Highly shape-selective guest encapsulation in the precisely defined cavity of a calix[4]arene-capped metalloporphyrin

Article abstract of DOI:10.1039/c1cc14739k

We developed a metalloporphyrin-based molecular container capped with a calix[4]arene, and its rigid cavity distinguished the slight structural differences in the aromatic guests. The Royal Society of Chemistry 2011.

Full text of DOI:10.1039/c1cc14739k

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COMMUNICATION
Highly shape-selective guest encapsulation in the precisely defined cavity
of a calix[4]arene-capped metalloporphyrinw
Hajime Iwamoto,*a Saori Nishib and Takeharu Haino*b
Received 1st August 2011, Accepted 12th October 2011
DOI: 10.1039/c1cc14739k
We developed a metalloporphyrin-based molecular container
capped with a calix[4]arene, and its rigid cavity distinguished
the slight structural differences in the aromatic guests.
In nature, the highest levels of molecular recognition events
are found, and include substrate recognitions by an enzyme,
ligand–acceptor interactions and antigen–antibody reactions.
The development of an artificial host, capable of binding
certain guest molecules with high specificity, has received
considerable attention with the goal of understanding the
mechanism of biomolecular recognition.1 However, there are
Fig. 1 Calix[4]arene-capped porphyrin.
To investigate the guest-binding ability of calix[4]arene-
a very limited number of examples in the literature where
capped porphyrin 1Zn and Zn(II)-meso-tetraphenylporphyrin,
clear-cut selectivity and specificity for recognition are equal
to those of an enzymatic system.2 Although a number of
ZnTPP, titration experiments with N-containing aromatic
compounds in chloroform were carried out using electronic
absorption spectroscopy. The association constants (Kas)7 and
calixarene–porphyrin hybrids that mimic cytochrome P-450
have been created, the selectivity for their guest recognitions
was not comparable with that in nature.3,4 Herein, we report
the synthesis and the unusual guest selectivity of the new
molecular container 1Zn composed of calix[4]arene and
Zn(II)-porphyrin (Fig. 1).
binding free energies (DGs) for pyridine (7), 4-methylpyridine
(8), imidazole (9) and N-methylimidazole (10) were determined
(Table 1).
Surprisingly high guest selectivity is found for 1Zn. The
binding abilities of 7 and 9 are extremely higher than those of 8
and 10. Since the free energy differences (DDGs) of 19.6 and
35.8 kJ molꢀ1 are particular for 7 vs. 8 and 9 vs. 10 upon
complexation, the presence of the methyl groups on the guest
aromatic rings leads to the significant reduction of the guest
binding abilities. By contrast, no particular selectivity is
claimed in the guest complexation of ZnTPP. It is obvious
that the calix[4]arene moiety is responsible for developing the
shape selective discrimination of the host 1Zn.8
The synthesis of calix[4]arene-capped porphyrin 1Zn is
shown in Scheme 1. Treatment of methyl 2-formylbenzoate
25 with excess pyrrole under acidic conditions gave phenyl-
dipyrromethane derivative 3. Condensation of 3 with benzal-
dehyde in the presence of a catalytic amount of trifluoroacetic acid,
followed by oxidation with DDQ, afforded free-base porphyrin
4. Hydrolysis of 4 gave 5,15-bis(2-carboxy-1-benzyl)-10,20-
diphenylporphyrin, which was converted to acid chloride 5 using
oxalyl chloride. The coupling of 5 and diaminocalix[4]arene 66
furnished the desired calix[4]arene-capped porphyrin 1H2, which
was treated with excess amount of Zn(OAc)2 to give Zn(II)-
porphyrin derivative 1Zn.
a Department of Chemistry, Graduate School of Science and
Technology, Niigata University, 2-8050 Ikarashi, Nishi-ku, Niigata
950-2181, Japan. E-mail: iwamoto@chem.sc.niigata-u.ac.jp;
Fax: +81-25-262-6363; Tel: +81-25-262-6363
b Department of Chemistry, Graduate School of Science, Hiroshima
University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan.
E-mail: haino@sci.hiroshima-u.ac.jp; Fax: +81-82-424-0724;
Tel: +81-82-424-7427
w Electronic supplementary information (ESI) available: Experimental
section, NMR spectra of new compounds, the results of UV-Vis titration,
a NOESY and an EXSY spectrum of a mixture of 1Zn and pyridine, and
atomic coordinates of 1Zn with pyridine or imidazole. See DOI: 10.1039/
c1cc14739k
Scheme 1 Reagents and conditions: (a) pyrrole, TFA, 40%; (b) benzal-
dehyde, TFA, CH2Cl2; then DDQ, CH2Cl2, 17%; (c) LiOH, THF,
H2O, 92%; (d) (COCl)2, CH2Cl2; (e) 6, Et3N, CH2Cl2, 2 steps 22%; (f)
Zn(OAc)2, MeOH, CHCl3, 74%.
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12670 Chem. Commun., 2011, 47, 12670–12672
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Table 1 Association constants Ka (Mꢀ1) and binding free energies DG (kJ molꢀ1) in CHCl3 at 298 K and volumes (A3) of guest molecules
1Zn
ZnTPP
Ka
ꢀDG
Ka
ꢀDG
Guest
Volume
Pyridine (7)
74
87
64
77
53 400 ꢁ 800
20 ꢁ 1
27.0
7.4
35.8
0
2700 ꢁ 700
6000 ꢁ 230
7600 ꢁ 300
6800 ꢁ 300
19.6
21.6
22.1
21.9
4-Methylpyridine (8)
Imidazole (9)
N-Methylimidazole (10)
1 920 000 ꢁ 400 000
n.d.a
a
Association constant was too small to be determined.
Fig. 2 1H-NMR spectra (600 MHz) in chloroform-d at 298 K. (a) 1Zn (1.33 mM) and pyridine (7) (2.66 mM); (b) 1Zn (1.47 mM) and imidazole
(9) (4.41 mM). The signals of the free and encapsulated guests are marked with o and *, respectively.
To obtain a detailed understanding of the unusual shape
selectivity of 1Zn, the complex structures of the calix[4]arene-
capped porphyrin 1Zn with 7, 8, 9 and 10 were examined by
1H-NMR titration. The 1H-NMR spectra of 7 and 9 in the
presence of 1Zn showed two sets of the aromatic signals,
which were assigned to the protons of the free and bound
guests (Fig. 2a and b), whereas the protons of 8 and 10 slightly
shifted upfield to bring the time-averaged signals, arising from
a rapid exchange of the free and bound states (see ESIw). The
large complexation induced upfield shifts were observed only
for the protons of 7 and 9 (7: ꢀ8.2, ꢀ6.5 and ꢀ5.3 ppm for Ha,
Hb and Hg; 9: ꢀ7.3, ꢀ7.3 and ꢀ4.5 ppm for H0a, Ha, and Hb,
respectively), and were obviously larger than those observed
for the guests bound to ZnTPP.9,10 The calix[4]arene-capped
face is more shielded than the other side; thus, these large
upfield shifts place the guests inside the cavity. The close
contact of 7 and the calix[4]arene was proven by the inter-
molecular NOEs (see ESIw).
estimated to be 64–87 A3.13 1Zn recognizes the tiny changes of
the guest shapes. The strict shape selectivity for the guest
encapsulation can be rationalized using the calculated structures
of the host–guest complexes in Fig. 3. The two aromatic rings
connected to the porphyrin ring lean inward to squeeze the
planar guest, while the other two aromatic rings are tilted
outward. The two 3-position protons of the pyridine ring face
toward the aromatic ring that is tilted outward, resulting in
CH–p interactions. The calculations of complexes show that
pyridine coordination inside the host cavity is energetically
more preferable than that from outside of the cavity (DDH =
73.67 kJ molꢀ1). Thus, van der Waals attractive interactions in
the cavity play an important role in the face selectivity.14,15
The Hg of the pyridine is positioned close to the oxygen atoms
of the calix[4]arene lower rim. When a methyl group is
substituted for the proton Hg, the methyl group should create
the serious steric interactions against the oxygen atoms of the
The in–out guest exchange rate constants for pyridine were
determined by an exchange (EXSY)11 NMR experiment. DGzs
of 49.9 and 74.9 kJ molꢀ1 for the uptake and release of the
encapsulated guest are unexpectedly high. Accordingly, 1Zn
selectively encapsulates 7 within the cavity, which is released
through the small portals of the host, even though the
uncapped face of the porphyrin ring is sterically accessible
for the guest coordination.
To discuss the unusual shape selectivity of 1Zn, the molecular
modeling of the complexes was carried out by DFT calculation
using M06-2X/LANL2DZ.12 The volumes of the guests were
Fig. 3 Stereoplot of the optimized structure of the encapsulation
complex with 1Zn and pyridine. To simplify and clarify the calculation,
n-propyl groups were replaced with methyl groups.
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calix[4]arene that probably result in a large reduction of the
host–guest association.
better selectivities to Me-substituted guests and broader selectivities to
N-containing aromatic guests than 1Zn.
9 Complexation induced shifts of pyridine with ZnTPP were estimated
to be ꢀ6.1, ꢀ1.8 and ꢀ1.4 ppm for Ha, Hb and Hg, respectively.
10 Pyridine encapsulated by calix[4]arene experiences a upfield shift,
see: R. G. Chapman, G. Olovsson, J. Trotter and J. C. Sherman,
J. Am. Chem. Soc., 1998, 120, 6252–6260; N. P. Power,
S. J. Dalgarno and J. L. Atwood, New J. Chem., 2007, 31, 17–20.
11 Rate constants were calculated using the 2D EXSY program:
E. W. Abel, T. P. J. Coston, K. G. Orrell, V. Sik and
D. J. Stephenson, Magn. Reson., 1986, 70, 34–53. Change of
mixing time between 0.2 and 1.2 s did not influence considerably
the values of rate constants for pyridine.
In summary, axial ligands, such as pyridine and imidazole,
are known to bind to Zn(II)-porphyrins to give five-coordi-
nated complexes.16 In the case of capped porphyrins, axial
ligands can bind from either side of the porphyrin to give
positive association constants. Calix[4]arene-capped porphyrin
1Zn offers a guest-binding environment in its cavity to show
high guest selectivity. The guests that are shaped in a way that
is complementary to the confined cavity are capable of fitting
into and binding to the cavity by van der Waals attractive
interactions. This type of high shape selectivity is obviously
unusual in an artificial molecular host.
12 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone,
B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li,
H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng,
J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda,
J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao,
H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta,
F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin,
V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari,
A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi,
N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross,
V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts,
R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi,
C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma,
V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg,
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12672 Chem. Commun., 2011, 47, 12670–12672
This journal is The Royal Society of Chemistry 2011