A novel ditopic zinc-salophen macrocycle: A potential two-stationed wheel for [2]-pseudorotaxanes

Article abstract of DOI:10.1039/b613705a

Crown ether macrocycle 1 including a zinc-salophen unit is obtained via a de novo synthetic design to give a potential pH-driven two-stationed wheel component of [2]-pseudorotaxane systems. The Royal Society of Chemistry.

Full text of DOI:10.1039/b613705a

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www.rsc.org/obc | Organic & Biomolecular Chemistry
A novel ditopic zinc-salophen macrocycle: a potential two-stationed wheel for
[2]-pseudorotaxanes†‡
Antonella Dalla Cort,* Luigi Mandolini, Chiara Pasquini and Luca Schiaffino
Received 20th September 2006, Accepted 27th October 2006
First published as an Advance Article on the web 14th November 2006
DOI: 10.1039/b613705a
Crown ether macrocycle 1 including a zinc-salophen unit is obtained via a de novo synthetic design to
give a potential pH-driven two-stationed wheel component of [2]-pseudorotaxane systems.
bind a secondary ammonium ion by means of the crown ether
Introduction
oxygens (Fig. 1) and the corresponding deprotonated species
Considerable efforts in supramolecular chemistry and nanoscience
thanks to the ability of zinc-salophen compounds to form 1 : 1
complexes with amines.7 The peculiarity of the 5,5ꢀ junction of the
polyoxyethylene chain implies that one of the axial binding sites of
zinc is oriented inside the cavity pointing toward the chain. Such a
feature qualifies 1 as a candidate to act as a wheel in the formation
of [2]-pseudorotaxanes feasible of a pH promoted translocation
of a dialkylammonium axle between two stations. The status of
the system can be easily monitored thanks to the presence of the
zinc-salophen moiety that acts as a luminescent sensor.
have been devoted lately to the construction of dynamic molecular
assemblies whose movements can be controlled by external
stimuli.1 A number of studies in this field have been focused
on supramolecular systems that can be switched between two
stable states in the prospect for applications as memory units for
information storage of a single bit in binary code.2
Pseudorotaxanes formed by a crown ether and a dialkylammo-
nium cation belong to such systems, since the write–erase process
consists of a reversible threading–dethreading motion achieved by
pH changes1a,3 that can easily be detected by optical methods.4 As
a matter of fact, their practical application as nanoscale devices is
limited by the fact that one of the two states corresponds to the
disassembled components. To overcome this problem, many [2]-
rotaxanes have been developed in which the disassembling process
is prevented by the presence of bulky groups at the ends of the axle.
In this way, the deprotonation of the ammonium group does not
lead to dissociation, but it promotes the shuttling of the wheel to
another station positioned on the axle itself.5 A quite different
approach is the one adopted by Sauvage and coworkers who
prepared an electrochemically driven [2]-rotaxane system based
on the Cu(II)–Cu(I) couple, in which the molecular axis contains a
2,2ꢀ-bipyridine motif and the wheel a 1,10-phenanthroline and
a trispyridine unit. Depending on its oxidation state, copper
translocates between the two stations of the wheel, to coordinate
the bidentate chelate or the tridentate fragment.6
Fig. 1 Calculated structure of the complex between 1 and a dibenzylam-
monium cation.
Salophens are tetradentate ligands that bind strongly to metal
dications to form neutral complexes widely used as receptors,
catalysts, and carriers.8 These complexes are usually square planar
and one or two coordination sites are available on the central
metal for axial complexation of additional ligands. As far as we
know, in all macrocyclic metal salophen compounds reported in
the literature, the polyether chain connects either positions 3 and
3ꢀ of the side rings9 or two positions of the central ring,10 and in
both cases lies more or less on the same plane as the salophen
ligand. The consequence of this is that any species bound to the
polyether chain remains far from the axial coordination site of the
metal centre. Conversely, a chain connecting positions 5 and 5ꢀ
of the side rings has to pass above one of the faces of the planar
salophen moiety so that one axial coordination site of the metal
centre points toward the inside of the cavity. The appropriate chain
length was chosen on the basis of a computational study aimed at
establishing the right size to form a pseudorotaxane complex with
the dibenzylammonium cation.
Here we report on the newly synthesised zinc-salophen com-
plex 1 that represents a potential two stationed wheel for the
construction of dynamic systems in which the movement of the
axle is promoted by pH-changes rather than by electrochemical
stimuli. Actually, compound 1 is a ditopic receptor, since it can
Dipartimento di Chimica and IMC-CNR Sezione Meccanismi di Reazione,
Universita` La Sapienza, Box 34 Roma 62, 00185, Roma, Italy. E-mail:
antonella.dallacort@uniroma1.it; Fax: +3906490421; Tel: +390649913087
† Electronic supplementary information (ESI) available: Spectrophoto-
metric titrations, computational details and coordinates of calculated
structures. See DOI: 10.1039/b613705a
‡ The HTML version of this article has been enhanced with colour images.
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Scheme 1 Synthetic route to compound 1.
of 1 upon addition of dibenzylammonium methanesulfonate,
Fig. 3. UV–Vis titration experiments showed that association
is virtually quantitative (K > 106 M−1). Even larger spectral
changes are detected upon formation of the complex with neutral
dibenzylamine.
Results and discussion
Compound 1 was synthesised in three steps (Scheme 1) in reason-
able yield, from easily available starting materials. Introduction
of the methylene group between the aromatic rings and the first
oxygen atoms of the chain was essential to avoid slow oxidation
of the final product.
Unambiguous evidence for the formation of a strong complex
1
between 1 and a dibenzylammonium cation is provided by H
NMR spectra in CDCl3 (Fig. 2). In the spectrum of the free
macrocycle, the imine and benzyl protons appear as multiplets
(signals a and b of spectrum (i) in Fig. 2) which suggests the
coexistence of at least three slowly equilibrating species, possibly
corresponding to aqua complexes involving variable numbers of
water molecules. Upon addition of dibenzylammonium methane-
sulfonate (spectrum (ii) in Fig. 2) signals a and b turn into
sharp singlets. Consistent with the spectra of similar systems
available in the literature,9d,11 the resonances of the CH2N+ and
+
the NH2 protons of dibenzylammonium (signals B and C) are
shifted downfield and upfield, respectively, as a consequence of
the formation of N–H · · · O hydrogen bonds.
Fig. 3 Absorption and emission spectra (kex = 350 nm) at room
temperature in an air equilibrated CHCl3 solution of 1 (full lines),
1–dibenzylammonium complex (dashed lines), and 1–dibenzylammine
complex (dash–dotted lines). Concentrations are 5.4 × 10−5 M.
To verify the reversibility of the axle motion between the two
stations of the wheel, we used the classical protocol consisting of
successive additions of stoichiometric amounts of base and acid.1a
Since the association constant between 1 and dibenzylamine (K =
90 M−1, CHCl3, 25 ◦C) measured by UV–Vis titration is too
small to guarantee a high association degree, the less hindered
dipropylamine (K = 4500 M−1) was chosen to play the role
of the axle.12 The expectation is that after deprotonation, the
neutral secondary amine does not remain free in solution, but
is complexed by the metal centre either inside or outside the
cavity (Fig. 4). A molecular mechanics calculation carried out
utilising the force field MM3 indicates that in the gas phase,
inner complexation is favoured by 14.5 kcal mol−1 mainly due
to intra complex hydrogen bonding between the amino group of
dipropylamine and one of the oxygen atoms of 1 (Fig. 5). The
molecular motions were followed by 1H NMR spectroscopy on a
0.05 M solution of both components, a concentration at which the
Fig. 2 1H NMR spectra of (i) 1, (ii) 1–dibenzylammonium methane-
sulfonate, and (iii) dibenzylammonium methanesulfonate at 300 MHz in
CDCl3 at 298 K. Resonances a and b correspond to the imine and benzyl
protons in 1, respectively.
The formation of the complex is also confirmed by small
but detectable changes in both UV–Vis and fluorescence spectra
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Fig. 4 Schematic representation of the pH-driven motion of the dynamic
molecular system formed by compound 1 and a secondary ammonium
salt.
Fig. 6 1H NMR spectra at 300 MHz in chloroform at 25 ◦C: (i)
dipropylamine, (ii) 1–dipropylamine complex, (iii) after addition of 1 mol
equiv. of methanesulfonic acid, (iv) after addition of 1 mol equiv. of
Hu¨nig base, (v) 1–dipropylammonium complex. The signals labeled with
w represent water, the signal labelled with an asterisk belongs to the
protonated Hu¨nig base, and the signal labelled with d represents the methyl
group of the methanesulfonate anion.
concentrated hydrochloric acid (48 mL) were mixed and stirred
overnight. The solid that separated from the reaction mixture was
filtered, dissolved in diethyl ether, and dried over sodium sulfate.
Recrystallization from n-hexane afforded 2 in 50% yield. 1H NMR
(200 MHz, CDCl3, 25 ◦C) d 11.05 (s, 1H); 9.89 (s, 1H); 7.57–7.52
(m, 2H); 7.01–6.97 (d, 1H, J = 8.46 Hz); 4.58 (s, 2H).
Fig. 5 Calculated structure of the complex between 1 and dipropylamine
showing the intra complex hydrogen bond between the amino group of
dipropylamine and one of the oxygen atoms of 1.
5-[(2-{2-[2-(2-{2-[2-({3-formyl-4-hydroxybenzyl}oxy) ethoxy]
ethoxy} ethoxy) ethoxy]ethoxy}ethoxy)methyl]-2-hydroxybenzal-
dehyde (3). Sodium hydride 60% dispersion in mineral oil (1.07 g,
26.8 mmol) was placed under an argon atmosphere in a dry flask,
washed three times with n-hexane, and suspended in anhydrous
DMF (4 mL). The flask was then cooled with an ice bath and a
solution of hexaethylene glycol (1.06 g, 3.75 mmol) in anhydrous
DMF (4 mL) was slowly added. After the evolution of hydrogen
had ceased, 2 (1.30 g, 7.61 mmol) was slowly added. The resulting
yellow solution was stirred overnight at room temperature and
then poured over ice. After the ice had dissolved, the resulting
water solution was neutralized with 0.1 M hydrochloric acid and
extracted with two 25 mL portions of dichloromethane. The
organic layers were collected, washed with brine, and dried over
anhydrous sodium sulfate. Chromatographic purification of the
crude product (silica gel, 10% acetone in diethyl ether) afforded
association degree is calculated to be 93.5%. Association with 1
shifts downfield the resonances of all the amine protons (spectra
(i) and (ii) in Fig. 6). Addition of 1 mol equiv. of acid to the
1–amine complex (full arrows) converts this complex into the
pseudorotaxane (compare spectra (iii) and (v)). The subsequent
deprotonation of the dipropylammonium cation with use of 1 mol
equiv. of Hu¨nig base (dotted arrows) causes the amine to move
back to the metal centre (compare spectra (ii) and (iv)).
Experimental
Methods
1
1H NMR spectra were recorded with either a Bruker AC 200 or a
Bruker AC 300 spectrometer. UV–Vis spectra were recorded with
a Perkin Elmer Lambda 18 spectrophotometer. Luminescence
spectra were recorded with a Shimadzu RF-5001PC spectroflu-
orimeter.
the desired product as a colourless oil in 21% yield. H NMR
(200 MHz, CDCl3, 25 ◦C) d 10.98 (s, 2H); 9.88 (s, 2H); 7.55–7.47
(m, 4H); 6.98–6.93 (d, 2H, J = 8.51 Hz); 4.51 (s, 4H), 3.64 (m,
24H). 13C NMR (50 MHz, CDCl3) d = 197.4, 160.3, 138.3, 131.2,
130.0, 127.7, 115.3, 73.0, 71.3, 70.2 ppm.
Compound 1. A solution of 3 (0.102 g, 0.185 mmol) in
2.5 mL of dichloromethane and a solution of 1,2-diaminobenzene
(0.020 g, 0.184 mmol) in 2.5 mL of a 1 : 1 dichloromethane–
methanol mixture were added separately and simultaneously by
a syringe pump over 4 h to a solution of zinc acetate dihydrate
(0.046 g, 0.209 mmol) in 100 mL of refluxing methanol. The
mixture was refluxed for an additional 30 minutes and then sodium
carbonate (0.046 g, 0.434 mmol) was added. After cooling, the
reaction mixture was filtered, slowly concentrated under reduced
Materials
Solvents and chemicals were purchased from Aldrich and were
used as received. Hexaethylene glycol was prepared according to
a literature procedure.13
5-Chloromethyl-2-hydroxybenzaldehyde (2). According to an
already described procedure,14 salicylaldehyde (5.0 mL,
0.047 mol), formaldehyde 37 wt. % in H2O (3.6 mL), and
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pressure at room temperature to a volume of about 5 mL, and
kept overnight at −18 ◦C. Under these conditions, the product
precipitated as a yellow solid that was separated from the mother
liquor by filtration (0.029 g, yield 23%). Elemental analysis: calcd
(%) for C34H40N2O9Zn·3H2O: C, 55.27; H, 6.23; N, 3.79; found: C,
55.46; H, 6.01; N, 3.77. 1H NMR (200 MHz, acetone-d6, 25 ◦C) d
8.77 (bs, 2H); 7.88–6.75 (bm, 10H); 4.34 (bs, 4H); 3.76 (s, 2H);
3.60–3.09 (m, 22H). 13C NMR (50 MHz, CDCl3) d = 164.3,
158.9, 148.5, 136.1, 135.0, 129.7, 127.8, 122.9, 119.0, 116.8, 73.0,
71.3, 70.2 ppm. MS-ESI-TOF for C34H40N2O9Zn Na+ calcd: 707.2;
found: 707.3.
Galli for elemental analyses. We acknowledge MIUR, COFIN
2003, Progetto Dispositivi Supramolecolari for financial contribu-
tions.
References
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´
Computational details
Geometries of all the stationary structures were fully optimised
using the force field MM3 as implemented in Macromodel
version 6.0. Additional parameters have been introduced for zinc,
imine nitrogens, phenoxide oxygens, and imine hydrogens and
are reported in the ESI.† Partial atomic charges were computed
using the electrostatic potential (ESP) from the wavefunction
obtained by an AM1 calculation in SPARTAN version 5.0.1. A +2
charge was used for the zinc cation. These parameters gave good
agreement with X-ray structures of known complexes between
zinc-salophen compounds and amines.7
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In summary, we have synthesised and fully characterised the
new crown ether macrocycle 1 containing a zinc-salophen unit.
The novel design of this host, based on the 5,5ꢀ junction of the
polyoxyethylene chain, allows for the first time the isolation of a
metallomacrocycle in which the zinc orients one of its two axial
binding sites towards the inside of the cavity of the macrocycle to
face the crown ether chain. This compound behaves as a wheel in
the formation of [2]-pseudorotaxanes with secondary ammonium
ions. We found that the alternate addition of base and acid controls
guest shuttling between the two different binding sites of the
macrocycle. The future development of stoppering methodologies
compatible with the metal salophen moiety will lead to rotaxanes
in which the motion of the axle between the two stations will be a
“pure” intra-wheel translocation.
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Acknowledgements
We thank Ms Giorgia Magnatti for her assistance in the synthesis,
Prof. Alberto Credi for valuable discussions, and Dr Paola
14 S. J. Angyal, P. J. Morris, J. R. Tetaz and J. G. Wilson, J. Chem. Soc.,
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4546 | Org. Biomol. Chem., 2006, 4, 4543–4546
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