Novel crown ether and salen metal chelation driven molecular pincers

Article abstract of DOI:10.1021/ol061726o

The synthesis of novel metal chelation driven molecular pincers based on crown ether and salen ligand substructures are described. Their functionality was monitored by fluorescence spectroscopy using pyrene groups as fluorescence probes. The pincer was sh

Full text of DOI:10.1021/ol061726o

ORGANIC
LETTERS
2006
Vol. 8, No. 20
4537-4540
Novel Crown Ether and Salen Metal
Chelation Driven Molecular Pincers
Aki M. M. Abe, Juho Helaja,† and Ari M. P. Koskinen*
Laboratory of Organic Chemistry, Helsinki UniVersity of Technology, P.O.B. 6100,
FI-02015 TKK, Finland
ari.koskinen@hut.fi
Received July 13, 2006
ABSTRACT
The synthesis of novel metal chelation driven molecular pincers based on crown ether and salen ligand substructures are described. Their
functionality was monitored by fluorescence spectroscopy using pyrene groups as fluorescence probes. The pincer was shown to function
+
+
+
reversibly with respect to metal chelation with Zn2 and also to chelate ditopically with 100 mol % of Zn2 and 100 mol % Li or 200 mol %
of Li ion.
+
The control of molecular-scale mechanical movements is a
highly desired objective in the construction of molecular
devices and machines.1 When the movements generated are
related to opening, closing, and translocation functions, these
molecular-scale devices are often called molecular tweezers,2
scissors,3 hinges,4 or pincers.5 All of these systems exhibit
molecular units that are able to switch between two or more
states of geometry.
A convenient way to control molecular movements
between different geometries is metal chelation. Chelation
driven steering of conformation can be achieved using
pyridine,6 amine,4b and ether7 ligands. Additionally, crown
ethers have been widely applied as supramolecular binders
for cationic species, especially for alkali metals, since the
pioneering work of C. J. Pedersen.8,9
† Current address: Department of Chemistry, P.O. Box 55, FIN-00014,
University of Helsinki, Finland
(1) (a) Balzani, V.; Credi, A.; Raymo, F. M.; Stoddart J. F. Angew. Chem.,
Int. Ed. 2000, 39, 3348-3391. (b) Balzcmi, V.; Credi, A.; Venturi, M.
Molecular DeVices and Machines; Wiley-VCH: Weinheim, 2003.
(2) (a) Shinkai, S.; Nakaji, T.; Ogawa, T.; Shigematsu, K.; Manabe, O.
J. Am. Chem. Soc. 1981, 103, 111-115. (b) Kla¨rner, F.-G.; Kahlert, B.
Acc. Chem. Res. 2003, 36, 919-932.
(3) Muraoka, T.; Kinbara, K.; Kobayashi, Y.; Aida, T. J. Am. Chem.
Soc. 2003, 125, 5612-5613.
(4) (a) Tamaoki, N.; Norikane, Y. Org. Lett. 2004, 6, 2595-2598. (b)
Yuasa, H.; Miyagawa, N.; Izumi, T.; Nakatani, M.; Izumi, M.; Hashimoto,
H. Org. Lett. 2004, 6, 1489-1492.
Salens are widely applied strongly coordinating ligands
for a variety of transition metal ions. Their metal complexes
10.1021/ol061726o CCC: $33.50
© 2006 American Chemical Society
Published on Web 08/30/2006

have been used for many applications such as asymmetric
catalysis,10 sensing,11 and DNA cleavage.12 To the best of
our knowledge, however, thus far reversible Salen complex
formation has not been used to control molecular movements.
Reynolds and Reddinger have previously shown that the
closed ring Salen-crown ether molecules are able to perform
dual-ion cocomplexation;11a we instead extend this type of
ditopic metal chelation to open ring Salen-crown ether
molecules. Herein we report a novel molecular pincer
structure 1, in which Salen and crown ether functionalities
are combined to give a distinct closing and locking mech-
anism (and the driving force for the molecular pincer). The
proposed mechanism for this type of chelator is shown in
Figure 1. In the pincer molecule, the Salen moiety is the
Scheme 1
Salen fragment is built from 2,6-bis(hydroxymethyl)phenol
prior to their coupling to form the Salen crown backbone
(Schemes 1 and 2).
Scheme 2
Figure 1. Schematic illustration of metal chelation adjustable
molecular pincers. The structure on the left depicts ditopic metal
chelation.
primary metal chelator, in which phenolate groups act as
anionic binding sites (Figure 1). The crown ether part is an
additional tetradentate metal chelator.
To demonstrate the pincers’ functionality as a molecular
device we have equipped the Salen pincers with pyrene
groups to act as fluorescence reporters. By monitoring with
fluorescence spectroscopy it is possible to observe the open
and closed forms of the pincers: in a closed pincer structure,
the pyrene groups are brought into close proximity, affording
excimer fluorescence (Figures 1 and 2).13
For the pincer synthesis we have developed a concise two
directional synthetic strategy. The crown ether segment is
constructed from catechol and chloroethanol, whereas the
(5) Gromov, S. P.; Fedorova, O. A.; Ushakov, E. N.; Buevich, A. V.;
Baskin, I. I.; Pershina, Y. V.; Eliasson, B.; Edlund, U.; Alfimov, M. V. J.
Chem. Soc., Perkin Trans. 2 1999, 7, 1323-1329.
(6) Petitjean, A.; Khoury, R.; Kyritsakas, N.; Lehn, J. J. Am. Chem. Soc.
2004, 126, 6637-6647 and references therein.
(7) Inouye, M.; Konishi, T.; Isagawa, K. J. Am. Chem. Soc. 1993, 115,
8091-8095.
(8) (a) Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 7017-7036. (b)
Pedersen, C. J. J. Am. Chem. Soc. 1970, 92, 386-391. (c) Pedersen, C. J. J.
Am. Chem. Soc. 1970, 92, 391-394.
2,6-Bis(hydroxymethyl)phenol 2 was treated with 2,2-
dimethoxypropane in the presence of p-TsOH to afford the
acetonide 3 in good yield. Oxidation of acetonide 3 with
PCC gave aldehyde 4 in an excellent yield. Aldehyde 4 was
treated with HBr gas, resulting simultaneous deprotection
and bromination of benzylic hydroxyl group. Benzyl bromide
5 was collected in an excellent yield (Scheme 1).
(9) van Veggel, F. C. J. M.; Verboom, W.; Reinhoudt, D. N. Chem. ReV.
1994, 94, 279-299 and references therein.
(10) (a) Jacobsen, E. N.; Zhang. W.; Muci, A. R.; Ecker, J. R.; Deng, F.
J. Am. Chem. Soc. 1991, 113, 7063-7064. (c) Konsler, R. G.; Karl, J.;
Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120, 10780-10781.
(11) (a) Reddinger, J. L.; Reynolds, J. R. Chem. Mater. 1998, 10, 3-5.
(b) Shamsipur, M.; Yousefi, M.; Hosseini, M.; Ganjali, M. R.; Sharghi, H.;
Naeimi, H. Anal. Chem. 2001, 73, 2869-2874.
(12) (a) Gravert, D. J.; Griffin, J. H. J. Org. Chem. 1993, 58, 820-822.
(b) Routier, S.; Bernier, J-. L.; Catteau, J-. P.; Colson, P.; Houssier, C.;
Rivalle, C.; Bisagni, E.; Bailly, C. Bioconjugate Chem. 1997, 8, 789-792.
(13) de Silva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson, T.; Huxley,
A. J. M.; McCoy, C. P.; Rademacher, J. T.; Rice, T. E. Chem. ReV. 1997,
97, 1515-1566.
1,2-Bis(2-hydroxyethoxy)benzene 6 was prepared accord-
ing to a literature procedure.14 Product 7 was obtained in
(14) Bogaschenko, T.; Basok, S.; Kulygina, C.; Lyapunov, A.; Luky-
anenko, N. Synthesis 2002, 15, 2266.
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Org. Lett., Vol. 8, No. 20, 2006

Figure 2. UV-vis spectra of the titration measurements. (A) Fluorescence spectral change of 8 (10 µM in 1:1 MeOH/THF, excitation at
347 nm) upon addition of Zn(ClO4)2‚6H2O (0, 10, 20, 30, 40. 50, 60, 70, 80, 90, 100 mol %). (B) Fluorescence spectral change of 8-Zn2+
complex (10 µM in 1:1 MeOH/THF, excitation at 347 nm) with the addition of EDTA (0, 10, 20, 30, 40. 50, 60, 70, 80, 90, 100, 110, 120
mol %). (C) Fluorescence spectral change of 8-Zn2+ complex (10 µM in 1:1 MeOH/THF, excitation at 347 nm) with the addition of LiCl
(0, 10, 20, 30, 40. 50, 60, 70, 80, 90, 100, 110, 120, 130 mol %). (D) Fluorescence spectral change of 8 (10 µM in 1:1 MeOH/THF,
excitation at 347 nm) with the addition of LiCl (0, 10, 20, 30, 40. 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200,
210, 220, 230 mol %).
modest yield, by reaction of the sodium alcoholate of
hydroxyethoxybenzene 6 with benzaldehyde 5. The crown-
Salen hinge with pyrene functionalities (8) was prepared by
treating aldehyde 7 with 1-pyrenemethylamine (Scheme 2).
The pincer functionality and metal chelation ability of
compound 8 was studied in MeOH/THF (1:1) solution by
fluorescence spectroscopy. Without a chelated metal, com-
pound 8 gave only weak fluorescence when excited at 347
nm. However, when the solution was titrated with metal ions
an intense emission was observed at 475 nm. In the case of
Zn(ClO4)2 the emission intensity increased until the concen-
tration of ions reached 100 mol % (Figure 2A).
The reversibility of pincer function was tested by titration
with EDTA, which is known to trap transition metal ions.
The zinc complex 9 was titrated by portion-wise addition of
EDTA to the pincer-Zn2+ complex solution. Upon titration,
the fluorescence intensity decreased smoothly in an inverse
manner compared to titration of 8 with Zn2+. When 100 mol
% of EDTA had been added the fluorescence intensity
returned to the level of nonchelated 8 (Figure 2B).
The ditopic chelation ability of 8 was studied by adding
LiCl to the pincer-Zn2+ complex solution. Upon titration,
the emission fluorescence intensity dropped until 100 mol
% of the metal ion had been added and then remained stable.
We interpret this as being a consequence of Li+ coordination
to the crown ether moiety, causing a disturbance in the pyrene
excimer structure of 10, lowering the observed fluorescence
intensity (Figure 2C).
Titration of 8 with LiCl indicated that ditopic chelation is
also possible with a single metal ion: upon LiCl titration of
8 the emission intensity increased linearly until 200 mol %
of LiCl was added (Figure 2D).
In summary, we have introduced a molecular pincer based
on a reversible metal chelation driven Salen-crown ether
Org. Lett., Vol. 8, No. 20, 2006
4539

concept. It should be possible to use a number of primary
amines in the formation of the Schiff base Salen structure,
thus creating a library of related pincer structures. Currently,
we are studying how these pincers could be integrated into
macroscopic structures and be employed in advanced materi-
als.
acknowledge Prof. Olli Ikkala (Helsinki University of
Technology), Dr. Markus B. Linder, and M.Sc. Katri
Laurikainen (VTT) for assistance.
Supporting Information Available: Experimental pro-
cedures for the preparation of compound 8 and characteriza-
tion for new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
Acknowledgment. This work was financially supported
by the Finnish National Technology Agency. We gratefully
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