Lee et al.
JOCArticle
an effective method for mimicking the carbohydrate recog-
nition in nature is still needed to develop artificial carbohy-
drate receptors.
Results and Discussion
Design and Synthesis of Porphyrin-Based Receptors. As
envisioned from the X-ray structures of sugar-protein
complexes, an effective approach to carbohydrate recogni-
tion is to surround the polar hydroxyl groups of carbohy-
drates with complementary hydrogen-bonding groups and
introduce aromatic surfaces into the receptor against carbo-
hydrate CH moieties. This can be effectively realized in
porphyrin-based carbohydrate receptors with a preorga-
nized complementary and convergent arrangement of hydro-
gen-bond donor and acceptor functionalities in the RRRR-
positions of the porphyrin, along with a rigid platform
(porphyrin skeleton) providing aromatic surfaces for CH-π
interaction. Eight porphyrin-based receptors were prepared
for carbohydrate recognition, as illustrated in Chart 1. In
a series of urea-appended porphyrins, benzyl groups were
introduced in 1a and 1b, phenyl groups in 1c and 1d, and
methyl benzoate groups in 1e and 1f. By varying the attached
groups in this way, we could investigate how the binding
properties of porphyrins were affected by the attached groups.
Carbamate-appended porphyrin 1g and amide-appended
porphyrin 1h were also prepared to compare the hydrogen-
bonding ability of a urea group with that of carbamate and
amide groups toward carbohydrates.
The receptors were synthesized from meso-RRRR-tetrakis-
(o-aminophenyl)porphyrin, which was prepared by Collman’s
method,9a followed by Lindsey’s atropisomerization method.9b
Urea-appended porphyrins were synthesized from the reaction
between meso-RRRR-tetrakis(o-aminophenyl)porphyrin and
appropriate isocyanates that were commercially available or
generated in situ.10 Commercially available carbobenzoxy
chloride and phenylpropionyl chloride were utilized for the
preparation of 1g and 1h, respectively. Zinc porphyrins were
prepared in quantitative yields from free-base porphyrins and
Zn(OAc)2 in a mixture of chloroform and methanol. All of the
compounds were characterized by 1H NMR, 13C NMR, high-
resolution mass spectrometry, and elemental analysis.
Binding Affinities of the Receptors for Carbohydrates.
UV-vis absorption experiments in chloroform showed that
the Soret band of the receptors underwent a slight shift or was
changed in intensity as the carbohydrates were bound in the
inner space of the receptors. Without adding a large excess of
carbohydrate, clear isosbestic points were observed, which
indicatesthe existenceoftwo states throughthe formationof a
1:1 complex. This was also confirmed by a Job’s plot in the 1H
NMR experiments. The apparent association constants for
the formation of the complexes of receptors (1a-h) and various
carbohydrates (2-6) were estimated by fitting the curve of the
absorbance at λmax as a function of the change in carbo-
hydrate concentration to a 1:1 binding isotherm (Table 1).
As shown in Table 1, the receptors showed high affinities
for carbohydrates, and a general trend was seen in their
affinities for guests in the order 4 ≈ 2 > 3 > 5 > 6. Uridine
and thymidine derivatives 5 and 6 having a ribose unit
Recently, we reported the synthesis of aspartate urea-
appended porphyrins that displayed the highest current
levels of binding for octyl pyranosides in chloroform.7 In
addition, Bonar-Law and co-workers found that analogous
urea-appended porphyrins exhibited excellent affinity for
various carbohydrates.8 In the present study, we have con-
ducted systematic studies to develop a method that can be
used to control the binding affinities by varying the func-
tional groups on the periphery of the porphyrin and eluci-
dated the binding modes using various spectroscopic
techniques and computer-assisted modeling. In this paper,
we describe the syntheses and binding properties of porphyrin-
based receptors 1a-h with regard to monosaccharides
and the binding modes between the selected receptors and
monosaccharides.
(5) For recent studies in aqueous or partial aqueous media, see:
(a) Morales, J. C.; Penades, S. Angew. Chem., Int. Ed. 1998, 37, 654–657.
(b) Sugasaki, A.; Ikeda, M.; Takeuchi, M.; Shinkai, S. Angew. Chem., Int. Ed.
2000, 39, 3839–3842. (c) Hamachi, I.; Nagase, T.; Shinkai, S. J. Am. Chem.
Soc. 2000, 122, 12065–12066. (d) Bielecki, M.; Eggert, H.; Norrild, J. C. J.
Chem. Soc., Perkin Trans. 2 1999, 449–455. (e) Davis, C. J.; Lewis, P. T.;
McCarroll, M. E.; Read, M. W.; Cueto, R.; Strongin, R. M. Org. Lett. 1999,
1, 331–334. (f) Lewis, P. T.; Davis, C. J.; Cabell, L. A.; He, M.; Read, M. W.;
McCarroll, M. E.; Strongin, R. M. Org. Lett. 2000, 2, 589–592. (g) Rusin, O.;
ꢀ
ꢀ
Kral, V. Chem. Commun. 1999, 2367–2368. (h) Kral, V.; Rusin, O.;
Charvatova, J.; Anzenbacher, P., Jr.; Fogl, J. Tetrahedron Lett. 2000, 41,
ꢀ
ꢀ
ꢀ
10147–10151. (i) Rusin, O.; Lang, K.; Kral, V. Chem.;Eur. J. 2002, 8, 655–
663. (j) Sugimoto, N.; Miyoshi, D.; Zou, J. Chem. Commun. 2000, 2295–2296.
(k) Klein, E.; Crump, M. P.; Davis, A. P. Angew. Chem., Int. Ed. 2005, 44,
298–302. (l) Tong, A.-J.; Yamauchi, A.; Hayashita, T.; Zhang, Z.-Y.; Smith,
B. D.; Teramae, N. Anal. Chem. 2001, 73, 1530–1536. (m) Striegler, S.; Dittel,
M. J. Am. Chem. Soc. 2003, 125, 11518–11524. (n) Hou, J.-L.; Shao, X.-B.;
Chen, G.-J.; Zhou, Y.-X.; Jiang, X.-K.; Li, Z.-T. J. Am. Chem. Soc. 2004,
126, 12386–12394. (o) Goto, H.; Furusho, Y.; Yashima, E. J. Am. Chem. Soc.
2007, 129, 9168–9174. (p) Zhao, J.; Davidson, M. G.; Mahon, M. F.; Kociok-
€
Kohn, G.; James, T. D. J. Am. Chem. Soc. 2004, 126, 16179–16186. (q) Zhao,
J.; Fyles, T. M.; James, T. D. Angew. Chem., Int. Ed. 2004, 43, 3461–3464. (r)
Ferrand, Y.; Crump, M. P.; Davis, A. P. Science 2007, 318, 619–622. (s) Cao,
H.; McGill, T.; Heagy, M. D. J. Org. Chem. 2004, 69, 2959–2966. (t) Wang,
Z.; Zhang, D.; Zhu, D. J. Org. Chem. 2005, 70, 5729–5732. (u) Schmuck, C.;
Schwegmann, M. Org. Lett. 2005, 7, 3517–3520. (v) Mazik, M.; Cavga, H. J.
Org. Chem. 2006, 71, 2957–2963. (w) Mazik, M.; Cavga, H. Eur. J. Org.
Chem. 2007, 3633–3638. (x) Pal, A.; Berube, M.; Hall, D. G. Angew. Chem.,
Int. Ed. 2010, 49, 1492–1495. (y) Ferrand, Y.; Klein, E.; Barwell, N. P.;
ꢀ
Crump, M. P.; Jimenez-Barbero, J.; Vicent, C.; Boons, G. J.; Ingale, S.;
Davis, A. P. Angew. Chem., Int. Ed. 2009, 48, 1775–1779. (z) Barwell, N. P.;
Crump, M. P.; Davis, A. P. Angew. Chem., Int. Ed. 2009, 48, 7673–7676.
(6) For recent studies in polar or apolar organic media, see: (a) Davis,
A. P.; Wareham, R. S. Angew. Chem., Int. Ed. 1998, 37, 2270–2273. (b)
Lecollinet, G.; Dominey, A. P.; Velasco, T.; Davis, A. P. Angew. Chem., Int.
Ed. 2002, 41, 4093–4096. (c) Velasco, T.; Lecollinet, G.; Ryan, T.; Davis,
€
A. P. Org. Biomol. Chem. 2004, 2, 645–647. (d) Bahr, A.; Droz, A. S.;
Puntener, M.; Neidlein, U.; Anderson, S.; Seiler, P.; Diederich, F. Helv.
€
Chim. Acta 1998, 81, 1931–1963. (e) Smith, D. K.; Zingg, A.; Diederich, F.
€
Helv. Chim. Acta 1999, 82, 1225–1241. (f) Bahr, A.; Felber, B.; Schneider, K.;
Diederich, F. Helv. Chim. Acta 2000, 83, 1346–1376. (g) Welti, R.; Diederich,
F. Helv. Chim. Acta 2003, 86, 494–503. (h) Inouye, M.; Takahashi, K.;
Nakazumi, H. J. Am. Chem. Soc. 1999, 121, 341–345. (i) Inouye, M.; Chiba,
K. J.; Nakazumi, H. J. Org. Chem. 1999, 64, 8170–8178. (j) Abe, H.; Aoyagi,
Y.; Inouye, M. Org. Lett. 2005, 7, 59–61. (k) Mazik, M.; Bandmann, H.;
Sicking, W. Angew. Chem., Int. Ed. 2000, 39, 551–554. (l) Mazik, M.; Sicking,
W. Chem.;Eur. J. 2001, 7, 664–670. (m) Mazik, M.; Radunz, W.; Sicking,
W. Org. Lett. 2002, 4, 4579–4582. (n) Mazik, M.; Radunz, W.; Boese, R. J.
Org. Chem. 2004, 69, 7448–7462. (o) Mazik, M.; Sicking, W. Tetrahedron
Lett. 2004, 45, 3117–3121. (p) Mazik, M.; Cavga, H.; Jones, P. G. J. Am.
Chem. Soc. 2005, 127, 9045–9052. (q) Ishi-i, T.; Mateos-Timoneda, M. A.;
Timmerman, P.; Crego-Calama, M.; Reinhoudt, D. N.; Shinkai, S. Angew.
Chem., Int. Ed. 2003, 42, 2300–2305. (r) Kim, H. -J.; Kim, Y. -H.; Hong, J. -I.
Tetrahedron Lett. 2001, 42, 5049–5052. (s) Cho, H.-K.; Kim, H.-J.; Lee,
K.-H.; Hong, J.-I. Bull. Korean Chem. Soc. 2004, 25, 1714–1716. (t) Lee,
D.-H.; Kim, H.-J.; Hong, J.-I. Supramol. Chem. 2007, 19, 251–256.
(9) (a) Collman, J. P.; Gagne, R. R.; Reed, C. A.; Halbert, T. R.; Long,
G.; Robinson, W. T. J. Am. Chem. Soc. 1975, 97, 1424–1439. (b) Lindsey,
J. S. J. Org. Chem. 1980, 45, 5215.
(10) Compounds 1c and 1d were previously synthesized and used as anion
receptors by Burns’ group: Jagessar, R. C.; Shang, M.; Scheidt, W. R.;
Burns, D. H. J. Am. Chem. Soc. 1998, 120, 11684–11692. 1c: HRMS calcd for
(7) Kim, Y.-H.; Hong, J.-I. Angew. Chem., Int. Ed. 2002, 41, 2947–2950.
(8) Ladomenou, K.; Bonar-Law, R. P. Chem. Commun. 2002, 2108–2109.
C72H55N12O4 m/z 1151.4469, found 1151.4447. 1d: HRMS calcd for
C72H52N12O4Zn m/z 1212.3526, found 1212.3536.
J. Org. Chem. Vol. 75, No. 22, 2010 7589