J. Am. Chem. Soc. 1999, 121, 10239-10240
10239
Scheme 1
Guest-Selected Formation of Pd(II)-Linked Cages
from a Prototypical Dynamic Library
Shuichi Hiraoka and Makoto Fujita*,†
Coordination Chemistry Laboratories
Institute for Molecular Science, CREST
Japan Science and Technology Cooperation (JST)
Myodaiji, Okazaki, 444-8585, Japan
ReceiVed March 8, 1999
Biological receptors modulate the shape and size of their
recognition sites to bind substrate molecules,1 generating numer-
ous receptor structures from which the most suitable one is
selected (or induced-fit) by their substrates. Modeling such a
system is particularly important to develop a new receptor design
wherein artificial receptors are constructed through a selection
process by their own guests. Although previous examples dealt
with the induced-fit control of receptor conformations, there are
only several reports on the control of receptor linkages.2 Here
we report the guest-selected formation of its optimal cage-like
receptor from an equilibrium mixture of receptors.3,4 In Scheme
1, Pd(II)-linked cages, 3 and 4, and some oligomeric compounds,5
accessible from the same components 1 and 2, are in equilibrium.
We show that, from this thermodynamic mixture, each cage
structure is selected upon the addition of appropriate guest
molecules. The phenomenon described herein is a prototype for
a “dynamic receptor library”,2 which represents one of important
goals in the field of molecular recognition.
The treatment of 1 with 2 in a 3:2 ratio first resulted in the
formation of a mixture of oligomeric compounds5 (Figure 1a).
From this mixture, however, cage complex 3 was selectively
formed upon the addition of 1,3,5-benzenetricarboxylic acid (5).6
1H NMR revealed the desymmetrization of both the host and the
guest frameworks (Figure 1b), in good agreement with the
asymmetric structure of 3. Namely, Hc and Hd of the host C6H3
ring, as well as Py1 and Py2 rings, were inequivalent and guest
† Present address: Department of Applied Chemistry, Graduate School of
Engineering, Nagoya University, Chikusa, Nagoya 464-8603, Japan; E-mail:
(1) Koshland, D. E., Jr. FEBS Lett. 1976, 62, E47.
(2) Several recent reports deal with the dynamic receptor library: (a)
Rowan, S. J.; Sanders, J. K. M. J. Chem. Soc., Perkin Trans. 1 1997, 1407.
(b) Brady, P. A. Sanders, J. K. M. J. Chem. Soc., Perkin Trans .1 1997, 3237.
(c) Hasenknopf, B.; Lehn, J.-M.; Boumediene, N.; Dupont-Gervain, A.;
Dorsselaer, A. V.; Kneisel, B.; Fenske, D. J. Am. Chem. Soc. 1997, 119, 10956.
(d) Rivera, J. M.; Mart´ın, T.; Rebek, J., Jr. J. Am. Chem. Soc. 1998, 120, 819.
(e) Lee, S. B.; Hwang, S.; Chung, D. S.; Yun, H.; Hong, J.-I. Tetrahedron
Lett. 1998, 39, 873. (f) Klekota, B.; Hammond, M. H.; Miller, B. L.
Tetrahedron Lett. 1997, 38, 8639. (g) Still, W. C. J. Org. Chem. 1998, 63,
904. (h) Also see: Goodman, M. S.; Jubian, V.; Linton, B.; Hamilton, A. D.
J. Am. Chem. Soc. 1995, 117, 11610.
(3) Guest-induced assembly of receptors: (a) Fujita, M.; Nagao, S.; Ogura,
K. J. Am. Chem. Soc. 1995, 117, 1649. (b) Bilyk, A.; Harding, M. M. J.
Chem. Soc., Chem. Commun. 1995, 1697.
(4) Guest-templated synthesis of receptors: (a) Anderson, S.; Anderson,
H. L.; Sanders, J. K. M. Acc. Chem. Res. 1993, 26, 469. (b) Hoss, R.; Vo¨gtle,
F. Angew. Chem., Int. Ed. Engl. 1994, 33, 375. (c) Amabilino, D. B.; Stoddart,
J. F. Chem. ReV. 1995, 95, 2725.
Figure 1. 1H NMR observation of the guest-selected formation of cage
complexes (500 MHz, D2O, 25° C): (a) oligomeric mixtures obtained
from 1 and 2 in D2O ([1]0 ) 90 mM, [2]0 ) 60 mM); (b) 3‚5 complex
assembled upon the addition of 5 ([1]0 ) 90 mM, [2]0 ) 60 mM, [5]0 )
30 mM); (c) 4‚6 complex assembled upon the addition of an excess
amount of 6 (suspended) ([1]0 ) 12.5 mM, [2]0 ) 8.3 mM).
(5) Our preliminary result implies that, in addition to M3L2-type structures
(3 and 4), dimeric M6L4 compounds is involved.
(6) Experimental details: see Supporting Information.
(7) (a) Host behavior: Although protons a and a′ do not exchange on the
NMR chemical shift time scale, they are correlated by NOESY, showing the
rapid fliping of the pyridine ring (which has protons a and a′) on the NOESY
time scale (mixing time: 300 ms). On the other hand, no NOESY corelation
is observed between Py1 and Py2, suggesting the exchange of these rings does
not take place even on the NOESY time scale. NOEs are not observed between
the host and the guest by NOESY. (b) Guest behavior: desymmetrization of
the guest C6H3 ring also shows that the rotation of the guest molecule in the
cavity is not allowed on the NMR time scale. On the other hand, only one
singlet signal is observed for benzene guest, suggesting the rapid spining of
the bernzene molecule in the 4‚benzene complex on the NMR time scale.
C6H3 protons were observed at δ 4.50 (∆δ ) 4.08, s, 2 H) and
δ 4.81 (∆δ ) 3.77, s, 1 H).7 These observations strongly
suggested the formation of 3 which tightly accommodated 5 in
its cavity. The formation of host-guest complex 3‚5 was also
supported by ESI-MS which showed prominent peaks for [3‚5-
10.1021/ja990733n CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/15/1999