ORGANIC
LETTERS
2
001
Vol. 3, No. 9
335-1337
Transmembrane Ion Conductance by an
Acyclic Bolaamphiphile
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Thomas M. Fyles,* Chi-wei Hu, and Ryan Knoy
Department of Chemistry, UniVersity of Victoria, Victoria, BC, Canada V8W 3P6
tmf@uVic.ca
Received February 14, 2001
ABSTRACT
An acyclic bolaamphiphile forms ion channels in vesicles and planar bilayer membranes that are closely similar to the channels formed by
related bismacrocyclic compounds. Thus the function of these ion channels does not depend on synthetically difficult macrocyclic subunits.
Most known examples of synthetic ion channels have
plausible to the extent that synthetic channels of high activity
have been designed using these principles. A few contrary
examples of flexible acyclic materials apparently form some
type of ion-conducting structure in bilayer membranes
without the supposed benefit of macrocyclic or rigid poly-
cyclic components. Apart from the scientific question of
whether the design assertions are sound, there is a consider-
able practical issue at stake: flexible acyclic compounds
would be easier to make than macrocycles bearing the same
structural elements.
1
,2
macrocyclic or polycyclic structural components. Such
components are claimed (by us and others) to be a useful
3
building-block motif to facilitate synthesis, to provide portals
4
for cation entry and transfer through the bilayer, and/or to
6
,7
provide rigidity to limit the conformations open to the
5
transporter. All of these factors are supposed to promote
the entry of the transporter into the bilayer and to provide
the structural integrity of the transmembrane pore. This is
(
1) Reviews: Gokel, G. W.; Murillo, O. Acc. Chem. Res. 1996, 29, 425-
We have reported the ion-transporting activity of a series
of bismacrocyclic bolaamphiphiles such as 1. Such com-
4
32. Fyles, T. M.; van Straaten-Nijenhuis, W. F. ComprehensiVe Supramo-
8
lecular Chemistry; Reinhoudt, D. N., Ed.; Elsevier Science: Amsterdam/
New York, 1996; Vol. 10, pp 53-77.
pounds readily insert into bilayers and open cation-selective
channels, and they can be modified to produce voltage-gated
(2) Recent reports: Merritt, M.; Lanier, M.; Deng, G.; Regen, S. L. J.
Am. Chem. Soc. 1998, 120, 8494-8501. Clark, T. D.; Buehler, L. K.;
Ghadiri, M. R. J. Am. Chem. Soc. 1998, 120, 651-656. Otto, S.; Osifchin,
M.; Regen, S. L. J. Am. Chem. Soc. 1999, 121, 7276-7277. Otto, S.;
Osifchen, M.; Regen, S. L. J. Am. Chem. Soc. 1999, 121, 10440-10441.
Tedesco, M. M.; Ghebremariam, B.; Sakai, N.; Matile, S. Angew. Chem.,
Int. Ed. 1999, 38, 540-543. Sakai, N.; Majumdar, N.; Matile, S. J. Am.
Chem. Soc. 1999, 121, 4294-4295. Baumeister, B.; Sakai, N.; Matile, S.
Angew. Chem., Int. Ed. 2000, 39, 1955-1958. Bandyopadhyay, P.; Janout,
V.; Zhang, L.; Sawko, J. A.; Regen, S. L. J. Am. Chem. Soc. 2000, 122,
9
pores. Counterbalancing these desirable functions is a
tedious and inelegant synthesis. Is the macrocycle synthesis
(6) Kunitake, T. Ann. N.Y. Acad. Sci. 1986, 471, 70-82. Menger, F.
M.; Davis, D. S.; Persichetti, R. A.; Lee, J.-J. J. Am. Chem. Soc. 1990,
112, 2451-2452. Kobuke, Y.; Ueda, K.; Sokabe, M. J. Am. Chem. Soc.
1992, 114, 7618-7622.
(7) Acyclic compounds can also act as membrane-disrupting agents:
Jayasuriya, N.; Bosak, S.; Regen, S. L. J. Am. Chem. Soc. 1990, 112, 5844-
5850. Nagawa, Y.; Regen, S. L. J. Am. Chem. Soc. 1991, 113, 7237-7240.
(8) Fyles, T. M.; Loock, D.; van Straaten-Nijenhuis, W. F.; Zhou, X. J.
Org. Chem. 1996, 61, 8866-8874.
(9) Fyles, T. M.; Loock, D.; Zhou, X. J. Am. Chem. Soc. 1998, 120,
2997-3003.
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2888-12889.
3) Cross, G. G.; Fyles, T. M.; James, T. D.; Zojaji, M. Synlett 1993,
49-460.
4) Gokel, G. W. Chem. Commun. 2000, 1-9. Hartgerink, J. D.; Clark,
T. D. Chem. Eur. J. 1998, 4, 1367-1372.
5) Sakai, N.; Brennan, K.; Weiss, L. A.; Matile, S. J. Am. Chem. Soc.
997, 119, 8726-8727.
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0.1021/ol015713g CCC: $20.00 © 2001 American Chemical Society
Published on Web 04/06/2001