Published on Web 03/08/2008
Screening of π-Basic Naphthalene and Anthracene Amplifiers
for π-Acidic Synthetic Pore Sensors
Shinya Hagihara, Ludovic Gremaud, Guillaume Bollot, Jiri Mareda, and
Stefan Matile*
Department of Organic Chemistry, UniVersity of GeneVa, GeneVa, Switzerland
Abstract: Synthetic ion channels and pores attract current attention as multicomponent sensors in complex
matrixes. This application requires the availability of reactive signal amplifiers that covalently capture analytes
and drag them into the pore. π-Basic 1,5-dialkoxynaphthalenes (1,5-DAN) are attractive amplifiers because
aromatic electron donor-acceptor (AEDA) interactions account for their recognition within π-acidic
naphthalenediimide (NDI) rich synthetic pores. Focusing on amplifier design, we report here the synthesis
of a complete collection of DAN and dialkoxyanthracene amplifiers, determine their oxidation potentials by
cyclic voltammetry, and calculate their quadrupole moments. Blockage experiments reveal that subtle
structural changes in regioisomeric DAN amplifiers can be registered within NDI pores. Frontier orbital
overlap in AEDA complexes, oxidation potentials, and, to a lesser extent, quadrupole moments are shown
to contribute to isomer recognition by synthetic pores. Particularly important with regard to practical
applications of synthetic pores as multianalyte sensors, we further demonstrate that application of the lessons
learned with DAN regioisomers to the expansion to dialkoxyanthracenes provides access to privileged
amplifiers with submicromolar activity.
Introduction
As far as practical applications are concerned, the grand vision
of synthetic ion channels and pores as sensors has failed to
deliver for decades. The problem is the persistent incompatibility
with multianalyte sensing in complex matrixes.3,4 This problem
amplifiers, molecules that can capture otherwise elusive analytes
after enzymatic signal generation and drag them into the pore
for signal transduction. 1,5-Dialkoxynaphthalene (1,5-DAN)
3
1
2
hydrazides are excellent amplifiers because they can capture
analytes containing ketones and aldehydes as hydrazones and
5
can use aromatic electron donor-acceptor (AEDA) interactions
was solved last year with the introduction of reactive signal
to be recognized by synthetic pores with π-acidic naphthalene-
3
,5-8
(
1) (a) Fyles, T. M. Chem. Soc. ReV. 2007, 36, 335-347. (b) Davis, A. P.;
Sheppard, D. N.; Smith, B. D. Chem. Soc. ReV. 2007, 36, 348-357. (c)
Davis, J. T.; Spada, G. P. Chem. Soc. ReV. 2007, 36, 296-313. (d)
Boudreault, P. L.; Voyer, N. Org. Biomol. Chem. 2007, 5, 1459-1465. (e)
Sisson, A. L.; Shah, M. R.; Bhosale, S.; Matile, S. Chem. Soc. ReV. 2006,
diimides (NDIs)
(Figures 1 and 2). With effective concen-
trations for pore inactivation down to the low micromolar range,
signal amplification by up to 4 orders of magnitude can be
3
,7,8
achieved with this approach.
Focusing on amplifier design,
3
1
1
6
3
7
1
5, 1269-1286. (f) Hector, R. S.; Gin, M. S. Supramol. Chem. 2005, 17,
29-134. (g) Koert, U.; Al-Momani, L.; Pfeifer, J. R. Synthesis 2004, 8,
129-1146. (h) Matile, S.; Som, A.; Sord e´ , N. Tetrahedron 2004, 60,
405-6435. (i) Gokel, G. W.; Mukhopadhyay, A. Chem. Soc. ReV. 2001,
0, 274-286. (j) Scrimin, P.; Tecilla, P. Curr. Opin. Chem. Biol. 1999, 3,
30-735. (k) Kobuke, Y.; Ueda, K.; Sokabe, M. J. Am. Chem. Soc. 1992,
14, 7618-7622. (l) Fuhrhop, J.-H.; Liman, U.; Koesling, V. J. Am. Chem.
the objective of this study was to explore the structural
variability of DAN amplifiers to identify, on the one hand, the
minimal structural changes detectable by synthetic pores and,
on the other hand, to find the best amplifiers. We report that a
process as complex as isomer recognition by synthetic pores is
clearly influenced by the basic principles of AEDA interactions
such as frontier orbital overlap, redox potentials, and, less
pronounced, quadrupole moments. Moreover, we demonstrate
Soc. 1988, 110, 6840-6845. (m) Tabushi, I.; Kuroda, Y.; Yokota, K.
Tetrahedron Lett. 1982, 23, 4601-4604.
(
2) (a) CreatiVe Chemical Sensor Systems; Schrader, T., Ed.; Topics in Current
Chemistry 277; Springer: Berlin, 2007. (b) Zhang, C.; Suslick, K. S. J.
Agric. Food Chem. 2007, 55, 237-242. (c) Hennig, A.; Bakirci, H.; Nau,
W. M. Nat. Methods 2007, 4, 629-632. (d) Vial, L.; Dumy, P. J. Am.
Chem. Soc. 2007, 129, 4884-4885. (e) Wright, A. T.; Anslyn, E. V. Chem.
Soc. ReV. 2006, 35, 14-28. (f) Guarise, C.; Pasquato, L.; De Filippis, V.;
Scrimin, P. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 3978-3982. (g) Rissin,
D. M.; Walt, D. R. J. Am. Chem. Soc. 2006, 128, 6286-6287. (h) Liu, J.;
Lu, Y. Angew. Chem., Int. Ed. 2006, 45, 90-94. (i) Buryak, A.; Severin,
K. J. Am. Chem. Soc. 2005, 127, 3700-3701. (j) Tamaru, S.; Kiyonaka,
S.; Hamachi, I. Chem.-Eur. J. 2005, 11, 7294-7304. (k) Alaejos, M. S.;
Garcia Montelongo, F. J. Chem. ReV. 2004, 104, 3239-3265. (l) Marquette,
C. A.; Degiuli, A.; Blum, L. J. Biosens. Bioelectron. 2004, 19, 433-439.
(4) (a) Matile, S.; Tanaka, H.; Litvinchuk, S. Top. Curr. Chem. 2007, 277,
219-250. (b) Litvinchuk, S.; Sord e´ , N.; Matile, S. J. Am. Chem. Soc. 2005,
127, 9316-9317. (c) Das, G.; Talukdar, P.; Matile, S. Science 2002, 298,
1600-1602.
(5) (a) Lokey, R. S.; Iverson, B. L. Nature 1995, 375, 303-305. (b) Gabriel,
G. J.; Iverson, B. L. J. Am. Chem. Soc. 2002, 124, 15174-15175. (c)
Vignon, S. A.; Jarrosson, T.; Iijima, T.; Tseng, H. R.; Sanders, J. M. K.;
Stoddart, J. F. J. Am. Chem. Soc. 2004, 126, 9884-9885. (d) Talukdar, P.;
Bollot, G.; Mareda, J.; Sakai, N.; Matile, S. J. Am. Chem. Soc. 2005, 127,
6528-6529.
(6) Mukhopadhyay, P.; Iwashita, Y.; Shirakawa, M.; Kawano, S.; Fujita, N.;
Shinkai, S. Angew. Chem., Int. Ed. 2006, 45, 1592-1595.
(7) Tanaka, H.; Litvinchuk, S.; Tran, D.-H.; Bollot, G.; Mareda, J.; Sakai, N.;
Matile, S. J. Am. Chem. Soc. 2006, 128, 16000-16001.
(8) Tanaka, H.; Bollot, G.; Mareda, J.; Litvinchuk, S.; Tran, D.-H.; Sakai, N.;
Matile, S. Org. Biomol. Chem. 2007, 5, 1369-1380.
(
m) Campanella, L.; Bonanni, A.; Finotti, E.; Tomassetti, M. Biosens.
Bioelectron. 2004, 19, 641-651. (n) Goddard, J.-P.; Reymond, J.-L. Curr.
Opin. Biotechnol. 2004, 15, 314-322. (o) Houseman, B. T.; Huh, J. H.;
Kron, S. J.; Mrksich, M. Nat. Biotechnol. 2002, 20, 270-274. (p) Lavigne,
J. J.; Anslyn, E. V. Angew. Chem., Int. Ed. 2001, 40, 3118-3130. (q) Toko,
K. Biosens. Bioelectron. 1998, 13, 701-709.
(
3) Litvinchuk, S.; Tanaka, H.; Miyatake, T.; Pasini, D.; Tanaka, T.; Bollot,
G.; Mareda, J.; Matile, S. Nat. Mater. 2007, 6, 576-580.
10.1021/ja078256t CCC: $40.75 © 2008 American Chemical Society
J. AM. CHEM. SOC. 2008, 130, 4347-4351
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