Molecular switch triggered by solvent polarity: Synthesis, acid-base behavior, alkali metal ion complexation, and crystal structure

Article abstract of DOI:10.1002/chem.200390090

The synthesis and characterization of the new tetraazamacrocycle L, bearing two 1,1′-bis(2-phenol) group as side-arms, is reported. The basicity behavior and the binding properties of L toward alkali metal ions were determined by means of potentiometric m

Full text of DOI:10.1002/chem.200390090

FULL PAPER
Molecular Switch Triggered by Solvent Polarity: Synthesis, Acid Base
Behavior, Alkali Metal Ion Complexation, and Crystal Structure
Gianluca Ambrosi,[a] Paolo Dapporto,[b] Mauro Formica,[a] Vieri Fusi,*[a] Luca Giorgi,[a]
Annalisa Guerri,[b] Mauro Micheloni,*[a] Paola Paoli,[b] Roberto Pontellini,[a] and
Patrizia Rossi[b]
Abstract: The synthesis and character-
ization of the new tetraazamacrocycle L,
bearing two 1,1'-bis(2-phenol) groups as
side-arms, is reported. The basicity be-
havior and the binding properties of L
toward alkali metal ions were deter-
mined by means of potentiometric
measurements in ethanol/water 50:50
(v/v) solution (298.1 Æ 0.1 K, I ˆ
0.15 moldmÀ3). The anionic HÀ1LÀ spe-
cies can be obtained in strong alkaline
solution, indicating that not all of the
acidic protons of L can be removed
under the experimental conditions used.
This species behaves as a tetraprotic
base (log K1 ˆ 11.22, log K2 ˆ 9.45, log
K3 ˆ 7.07, log K4 ˆ 5.08), and binds alkali
metal ions to form neutral [MHÀ1L]
complexes with the following stability
constants: log KLi ˆ 3.92, log KNa ˆ 3.54,
log KK ˆ 3.29, log KCs ˆ 3.53. The ar-
rangement of the acidic protons in the
HÀ1LÀ species depends on the polarity of
the solvents used, and at least one
proton switches from the amine moiety
to the aromatic part upon decreasing the
polarity of the solvent. In this way two
different binding areas, modulated by
the polarity of solvents, are possible in L.
One area is preferred by alkali metal
ions in polar solvents, the second one is
preferred in solvents with low polarity.
Thus, the metal ion can switch from one
location to the other in the ligand,
modulated by the polarity of the envi-
ronment. A strong hydrogen-bonding
networkshould preorganize the ligand
for coordination, as confirmed by MD
simulations. The crystal structure of the
[Na(HÀ1L)] ¥ CH3CN complex (space
group
20.205(3),
P21/c,
a ˆ 12.805(1),
b ˆ
c ˆ 14.170(2) ä,
b ˆ
100.77(1)8, Vˆ 3601.6(8) ä3, Z ˆ 4, R ˆ
0.0430, wR2 ˆ 0.1181), obtained using
CH2Cl2/CH3CN as mixed solvent, sup-
ports this last aspect and shows one of
the proposed binding areas.
Keywords: alkali metals ¥ molecular
dynamics
¥ molecular switches ¥
structure elucidation ¥ synthesis
external stimulation such as chemical,[12] electrochemical,[13]
and light inputs.[14] However, researchers in many other fields
are interested in applying these systems for molecular
recognition or in coordination chemistry, in which the system
switches adapting (or not) itself to recognize the substrate.[15]
Over the last few years, we have synthesized many cyclic
(macrocycles) and noncyclic ligands with one phenolic
function in their molecular framework.[16] Clearly many
different molecular topologies are possible; however, the
insertion of the phenolic group always strongly influences the
coordination and spectroscopic properties of the resulting
molecule. By joining phenolic oxygen with amine-nitrogen
donor atoms, it is possible to produce an internal separation of
negative and positive charges in the ligands depending on pH
values in aqueous solution;[17] in many cases, one of the acidic
protons in the free ligand or in the complex formed can switch
its position from a nitrogen to the oxygen atom of the phenol
and vice-versa, depending on the polarity of the solvent
used.[18] Moreover, when these ligands have lost all acidic
protons, they have a harder oxygen atom in the phenolate
group with softer amine nitrogen atoms. These aspects led us
Introduction
Macrocyclic compounds continue to attract the interest of
researchers in coordination chemistry.[1 Indeed, the count-
5]
less possible applications of these molecules, as well as their
usefulness in fundamental studies, have made this a thriving
field of research.[6 10] The synthesis of molecular switches is a
growing area because of the potential of these related systems
for use in carrying information and, eventually, in molecular
devices.[11] Several examples are based on systems whose
optical properties (such as photochromism, luminescence,
optical nonlinearity) can be switched or modulated by
[a] Prof. V. Fusi, Prof. M. Micheloni, Dr. G. Ambrosi, Dr. M. Formica,
Dr. L. Giorgi, Dr. R. Pontellini
¡
Istituto di Scienze Chimiche, Universita di Urbino
Piazza Rinascimento 6, 61029 Urbino (Italy)
Fax : (‡39)0722-350032
E-mail: vieri@chim.uniurb.it
[b] Prof. P. Dapporto, Dr. A. Guerri, Prof. P. Paoli, Dr. P. Rossi
¡
Dipartimento di Energetica ™S. Stecco∫, Universita di Firenze
via S. Marta 3, 50139 Firenze (Italy)
800
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800 810
to increase the number of phenolic groups while preserving a
high number of amine functions, with the aim of creating
softer and harder coordination areas in the ligand, and a high
number of spatially separated negative and positive charges.
Furthermore, the idea was to modulate these properties by
acting on the surrounding environment, by means of the pH
and/or the polarity of the medium, causing the ligand to adapt
to fulfil a specific purpose. Indeed, changes in the environ-
ment can produce profound modifications in the molecule,
forcing not only the protons but also a coordinated metal ion
to move from one region of the molecule to another,
producing a molecular switch. We recently reported a
synthetic pathway for the production of aza-macrocycles
containing a 1,1'-bis(2-phenol) fragment with two contiguous
phenolic groups.[19] Taking into account that no examples of
the coordination properties of biphenol toward metal cations
and only very few examples of it as an integral part of ligands
had previously been reported,[20] its coordination behavior
appeared interesting.
achieved. The basicity and binding properties of L towards
alkali metal ions were investigated in solvents with different
dielectric constants.
Results and Discussion
Synthesis: The synthetic pathway used to obtain L is depicted
in Scheme 1. The reagent 3-bromomethyl-2,2'-dimethoxybi-
phenyl (3) was synthesized starting from 1,1'-biphenol, the
hydroxy functions of which were protected with methyl
groups to give 1 as previously reported. The aromatic ring
was activated at the 3 and 3' positions by using butyllithium
and a methyl group was inserted by using dimethyl sulfate in
THF to give 2. The same reaction performed in diethyl ether
gave lower yield. The inserted methyl group was brominated
by using N-bromosuccinimide to afford the reagent 3. The
macrocycle 5 was obtained in high yield by reacting two
equivalents of 3 with the tetraaza macrocyclic base 4 in
CH3CN in the presence of a base. The demethylation of the
phenolic oxygen atom was carried out with a 48% acetic acid/
HBr mixture in the presence of phenol, affording macrocycle
L as the tetrahydrobromide salt, which was further purified by
recrystallization from methanol acetonitrile solution. Other
cleavage reactions of the methyl groups, using BBr3, LiAlH4,
or lithium in liquid NH3, led to an uncontrolled reaction.
Herein we report the synthesis of the new ligand 1,7-
bis[(2,2'-dihydroxybiphen-3-yl)methyl]-4,10-dimethyl-1,4,7,10-
tetraazacyclododecane (L). Ligand L was synthesized by
X-ray structure of [Na(HÀ1L)] ¥ CH3CN (6): The asymmetric
unit of [Na(HÀ1L)] ¥ CH3CN (6) contains a molecule of 6 and a
molecule of CH3CN, which are not involved in relevant
intramolecular contacts. The sodium cation is hexacoordinat-
ed by the four nitrogen atoms and the O1 and O3 oxygen
atoms of L. The coordination polyhedron can be described as
a distorted trigonal prism with the O1, N1, N2 and O3, N3, N4
atoms defining the two triangular faces, which are parallel
À
within 6.94(6)8 (Figure 1, Table 1). The Na N distances fall in
attaching two 1,1'-bis(2-phenol) groups to a tetraaza macro-
cycle. In this way we introduced a high number of phenolic
groups into an amine skeleton capable of producing two
different hard and soft coordination areas. Moreover, a high
degree of separation of positive and negative charges was
the range 2.467(2) 2.520(2) ä and are significantly shorter
than those found for sodium complexes of cyclen derivatives
(a search performed in the Cambridge Structural database
(CSD) v5.22[21] showed that the range for Na N distances in
the 13 complexes retrieved is 2.532 2.726 ä). The two Na O
À
À
Scheme 1. Synthesis of L.
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V. Fusi, M. Micheloni et al.
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retrieved. The overall structures of 6 and LiBN2O6 are very
similar in that both feature: 1) the quite common [3333] C
corners[23] conformation for the [12]aneN4[24] and [12]aneN2O2
rings; 2) the aromatic arms folded towards the macrocyclic
cavity with a head-to-tail arrangement; 3) a very similar
coordination polyhedron around the two alkali cations. This
similarity may be ascribed to the intramolecular interaction
involving the oxygen atoms of the aromatic moieties. In fact,
in compound 6 there are three short intramolecular hydrogen
bonds (Table 2) that involve two oxygen atoms (O2 and O4)
and three hydrogen atoms (H10, H20, and H30). Interestingly,
À
À
the O2 H20 and O4 H20 distances are comparable, that is
the H20 atom is almost equidistant, within 3s, between O2
and O4, whereas in LiBO6N2 the four oxygen atoms of the
catechol moieties are held together by the boron atom. In the
solid-state structure of compound 6 no relevant intermolec-
ular contacts are present.
Figure 1. Structure of compound 6 (ORTEP view).
Table 1. Selected bond lengths [ä] and angles [8] for 6.
Table 2. Intramolecular hydrogen-bond lengths [ä] and angles [8] for
compound 6.
À
O1 H10
0.95(3)
1.14(4)
0.99(3)
H10 ¥¥¥ O2
H20 ¥¥¥ O4
H30 ¥¥¥ O4
1.65(3)
1.36(4)
1.51(3)
166(3)
167(3)
170(3)
À
O2 H20
À
À
Na1 O3
2.303(2)
2.467(2)
2.519(2)
85.82(5)
101.49(6)
124.35(6)
80.13(5)
74.75(6)
160.75(6)
73.84(6)
117.98(6)
Na1 O1
2.320(2)
2.470(2)
2.520(2)
120.08(6)
106.13(6)
116.35(6)
160.68(6)
72.78(6)
7.92(6)
À
O3 H30
À
À
Na1 N2
Na1 N4
À
O1 H10 ¥¥¥ O2
À
À
Na1 N3
Na1 N1
À
O2 H20 ¥¥¥ O4
O3-Na1-O1
O1-Na1-N2
O1-Na1-N4
O3-Na1-N3
N2-Na1-N3
O3-Na1-N1
N2-Na1-N1
N3-Na1-N1
O3-Na1-N2
O3-Na1-N4
N2-Na1-N4
O1-Na1-N3
N4-Na1-N3
O1-Na1-N1
N4-Na1-N1
À
O3 H30 ¥¥¥ O4
Solution studies, basicity
75.58(6)
Potentiometric study: Table 3 summarizes the basicity con-
stants of L, potentiometrically determined in 0.15 moldmÀ3
NMe4Cl ethanol/water 50:50 (v/v) solution at 298.1 K. The
mixed solvent was used to increase the solubility of the species
distances (2.320 and 2.303 ä) are also slightly shorter than
those observed for sodium complexes with 2,2'-binaphthol
À
derivatives (seven sodium complexes with Na O distances in
Table 3. Basicity constants (Log K) of L determined in 50:50 (v/v) H2O/
EtOH (0.15 moldmÀ3 NMe4Cl) at 298.1 K.
the 2.363 2.568 ä range were found in the CSD). Concerning
the conformation adopted by the biphenol moieties, we found
that the angles between the aromatic ring of the binaphthyl
units are 45.04(6) and 38.83(6)8 for (C12 C17)-(C18 C23)
and (C25 C30-(C31 C36), respectively.
Reaction
log K
‡
HÀ1LÀ ‡ H ! L
11.22(1)
9.45(1)
7.07(1)
5.08(1)
‡
‡
L ‡ H ! HL
HL ‡ H ! H2L2‡
‡
‡
‡
H2L2‡ ‡ H ! H3L3‡
To investigate the coordination behavior of L, the solid-
state structures of alkali cation complexes with the macro-
cyclic ligand frameworkoutlined in Scheme 2a were looked
up in the CSD. The structure of a binuclear lithium boron
complex[22] with the 1,7-aza,4-11-oxacyclododecane derivative
shown in Scheme 2b (from now on deonted as LiBN2O6) was
of L at around pH 7 in aqueous solution. The neutral form of
the ligand can, in principle, add four protons and dissociate
four protons; it behaves as a triprotic base and as a
monoprotic acid under the experimental conditions used.
Taking into account that the total number of sites on the
ligand that can be involved in the acid base processes is eight
(four nitrogen and four oxygen atoms), the acid base
behavior of L is rather unexpected. In fact, only four of the
sites are directly involved under our experimental conditions.
As shown in Table 3, L can be present in alkali solution as the
species HÀ1LÀ. Analyzing the protonation constants starting
from this anionic species, it was found that HÀ1LÀ behaves as a
rather strong base in the first protonation step (log ˆ 11.22)
and the basicity is rather regularly reduced by roughly two log
units for each step of protonation, as expected from the
increase in the positive charge×s repulsion as the molecule
Scheme 2. a) Searched ligand in CSD (X ˆ O, N). b) LiBN2O6.
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Molecular Switches
800 810
becomes more protonated. The last three acidic protons
present on the HÀ1LÀ1 species could not be removed under our
experimental conditions, suggesting a strong hydrogen-bond-
ing network, which stabilizes them in the molecule.
ment of the chromophores can be supposed in the HÀ1LÀ
species. In the spectra recorded in the presence of an excess of
NMe4OH, further changes were not observed, suggesting that
no other deprotonation process occurs in the chromophores
even at higher pH values.
1
UV/Vis and NMR spectroscopic studies: UV/Vis absorption
electronic spectra of L were obtained in ethanol/water solvent
at different pH values to determine the role of the phenolic
function in the acid base behavior of L. The spectra show
different wavelength maxima (lmax) in the field of pH 2 and
12.5. At pH 2 the H3L3‡ species is prevalent in solution, and
two bands with lmax ˆ 242 and 283 nm, having molar absorp-
tivities of e ˆ 7400 and 6900 cmÀ1 molÀ1 dm3 respectively, were
observed. At pH 12.5 the HÀ1LÀ species is prevalent in
These data can be merged with those obtained in H and
13C NMR experiments performed at different pH values in
CD3OD/D2O 50/50 (v/v) mixed solvent, which furnished more
information about the localization of the acidic protons in the
different protonated species; 1H 1H and 1H 13C NMR
correlation experiments were performed to assign all of the
signals. The trends in chemical shifts of the most significant
resonances, reported as a function of pH, are shown in
Figures 3a and 3b. The 13C NMR spectrum, recorded at pH 3,
where H3L3‡ is prevalent in solution, exhibits fifteen peaks at
d ˆ 42.6 (C1), 48.4 (C3), 52.8 (C4), 54.7 (C2), 117.2 (C13),
122.9 (C9), 123.2 (C15), 124.8 (C5), 126.2 (C7), 129.3 (C11),
solution, and the spectrum mainly exhibits one band at lmax
ˆ
316 nm (e ˆ 8500 cmÀ1 molÀ1 dm3). These differences are due
to the deprotonation of the phenolic group that occurred at
high pH values. In other words, the change in lmax is ascribed
to the presence of the phenol hydroxyl form at low pH values
and to the phenolate form at high pH values. By monitoring
the spectra on going from acidic to basic pH and plotting the
&
absorbance of the spectra at l ˆ 316 nm (Figure 2, ) versus
&
Figure 2. Absorbance values at l ˆ 316 nm ( ) and distribution diagram of
the protonated species ( ) of L as a function of pH, in 50:50 (v/v) ethanol/
water solution at 298.1 Æ 0.1 K with 0.15 moldmÀ3 Me4NCl as ionic
medium.
pH, it is possible to determine during which deprotonation
steps the biphenols lose the acidic protons. This is possible by
coupling the trend of the value of the absorbance ascribed to
the involvement of the chromophores in the deprotonation
processes with the distribution diagram of the species
obtained by potentiometric measurements (lines in Figure 2).
The absorbance at 316 nm is approximately zero at pH < 4,
while it increases at higher pH, reaching its maximum values
at pH 12.5. Taken together with the distribution diagram of
the species, the absorbance was found to increase with the
appearance of the H2L2‡ species, reaching a plateau from
approximately pH 5.8 to pH 6.5, then increasing again with
‡
the appearance of the HL species, and finally reaching
another plateau from pH 8.5 to pH 11.3. It was also found to
be only slightly perturbed in the presence of the HÀ1LÀ
species. Taking into account that the change in absorbance
is due to the deprotonation of phenol groups, this profile can
be attributed to a first deprotonation of the chromophores
that
occurred
in
the
H2L2‡
species
(e(lˆ316)
ꢀ
‡
3900 cmÀ1 molÀ1dm3) and a second deprotonation in HL
Figure 3. Experimental NMR chemical shifts of L in 50:50 (v/v) CD3OD/
D2O solution, as a function of pH. a) 13C NMR ; b) 1H NMR.
(e(lˆ316) ꢀ 7800 cmÀ1 molÀ1 dm3), while a very limited involve-
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V. Fusi, M. Micheloni et al.
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131.4 (C14), 133.3 (C16), 133.5 (C8, C10), 153.5 (C12), and
154.2 ppm (C6). The H NMR spectrum has a singlet at d ˆ
At the lowest pH values, where the fully protonated species
H4L4‡ should be present in solution, the most significant
change is due to the downfield shift of the H3 and H4 protons
(see Figure 3b) in the a-position to the nitrogen atoms
bearing the side arms, which indicates that the last proto-
nation step needed to obtain the full protonated species H4L4‡
takes place on these amine groups. In other words, the H3L3‡
species shows a distribution of the seven acidic protons as
depicted in Scheme 3. On increasing the pH to the range in
which the protonated species H2L2‡ is prevalent in solution
1
2.52 ppm, which integrates for six protons and is due to the
resonance signals of the H1 protons, a multiplet at d ˆ
2.95 ppm (8H, H3), a multiplet at d ˆ 3.31 ppm (8H, H2), a
singlet at d ˆ 3.61 ppm (4H, H4), a multiplet at d ˆ 6.97 ppm
(6H, H9, H13, H15), and a multiplet at d ˆ 7.23 ppm (8H, H8,
H10, H16, H14). The spectrum indicates a C2v-symmetrical
structure on the NMR time scale, which is preserved
throughout the pH range investigated.
Scheme 3. Location of acidic hydrogen atoms in the protonated species of L.
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Molecular Switches
800 810
(pH 5.5 7), the resonance signal of the aromatic carbon
atoms C12 shows a marked downfield shift. In contrast, an
upfield shift is observed for the C15 signals in the para
position to the phenolic oxygen atom (see Figure 3a),
suggesting that the deprotonation step takes place on the
oxygen atoms of the external phenol groups. This hypothesis
is in agreement with the UV/Vis measurements, which
indicate the involvement of biphenol chromophores in the
deprotonation processes on going from H3L3‡ to H2L2‡. In the
Scheme 3. However, the aromatic parts undergo perturbation,
as visible by the shift of the signals due to C6 and C12 and by
the UV/Vis experiments. Further addition of a base did not
produce substantial changes in the NMR spectra, indicating
that the three acidic proton residues are strongly stabilized,
probably because of a dense hydrogen-bonding network, as
suggested in Scheme 3 for the HÀ1LÀ species. Scheme 3
depicts the complete distribution of the acidic protons in the
different protonated species proposed by the UV/Vis and
NMR experiments.
‡
pH 7.5 9 range, where the HL species is predominant in
solution, many resonance signals undergo a shift. In the
13C NMR, the most relevant shifts are due to the C6 and C3
resonance signals, which shift downfield, and C2, C5, and C9,
which shift upfield. This contrasting behavior can be ex-
plained by taking into account that the UV/Vis measurements
suggest a further involvement of the phenol moieties in this
deprotonation step as well. Thus the deprotonation must take
place on the oxygen atom with C6 in the a-position, and as a
result of the effect of the deprotonation on the carbon signals
of the phenol, the signal of C6 shifts downfield, while C5 and
C9 in the ortho and para position, respectively, shift upfield.[25]
The shifts of C2 and C3 can be explained, in agreement with
the b-effect of the protonation of the polyamines,[26] by a
redistribution of one positive charge in the macrocyclic base,
which shifts from the methylated nitrogen atoms to the
nitrogen atoms bearing the biphenols. This leads to the proton
distribution depicted in Scheme 3. This hypothesis was con-
firmed by the trend of the 1H NMR aliphatic resonance
signals which, in the pH 7.5 9 range, show an upfield shift of
the signal of the H1 and H2 hydrogen atoms, while the
resonance signals of H4 and H3 shift downfield. Examination
of the spectra recorded in the pH range where the neutral
species L is prevalent (10 < pH < 11), revealed that the main
resonance signals moving in the 13C NMR spectra are the
resonance signals of C5 and C2, which shift downfield, and C3,
which shifts upfield. The trend in the shift of C5 and C2
suggests, as does the b-effect of the deprotonation of the
polyamines, the involvement of the nitrogen bearing the side
arms in the deprotonation process. In contrast, the trend of C3
leads us to suppose a new redistribution of charge involving
the protons located on the polyamine base, which increase the
positive charge on the methylated nitrogen atoms and
produce a downfield shift of the resonance signal of C3. This
hypothesis is in agreement with the simultaneous upfield shift
of the H4 and H3 resonance signals and the downfield shift of
As can be seen in Scheme 3, L shows an internal separation
of positive and negative charges in the species existing up to
pH 5. For example, the neutral species L has two ammonium
and two phenolate groups.
In conclusion, the insertion of two biphenol groups into a
polyamine macrocycle influences the disposition of the acidic
protons, permitting a separation of the positive and negative
charges in the polyprotonated species even at slightly acidic
pH values. For this reason, L offers promising possibilities for
use as a receptor for substrates, such as the simple amino
acids, which present a simultaneous separation of negative
and positive charges.
The anionic species HÀ1LÀ and the neutral species L are
also soluble in organic solvents with a lower dielectric
constant, such as CHCl3 or CH2Cl2. The spectra of the two
species in CHCl3 show approximately the same profile, with
two bands at 283 (e ꢀ 5000 cmÀ1 molÀ1 dm3) and 316 nm (e ꢀ
3700 cmÀ1 molÀ1 dm3) characteristic of the simultaneous pres-
ence of the phenolic and phenolate forms of the chromo-
phores. The molar absorptivities, compared with those
previously reported for the polar mixed solvent, indicate the
deprotonation of one phenol group; thus, as reported in
Scheme 3, it is possible to hypothesize a redistribution of the
acidic protons of HÀ1LÀ in solvents with low dielectric
constants. This distribution could easily be obtained by the
shift of the acidic proton located in the polyamine base in a
polar solvent. In this case, the low solvation power of an
apolar solvent leads to a lower separation of charge.
The NMR experiments confirmed this hypothesis. In fact,
1
comparison of the H NMR spectrum of the HÀ1LÀ species
recorded in a mixed polar solvent, such as as D2O/CD3OD,
with that of the same species recorded in CDCl3 revealed a
downfield shift of some of aromatic resonance signals in
apolar solvents coupled with an upfield shift of the aliphatic
1
resonance signals (Figure 4). These H NMR shifts indicate
1
H1 in the H NMR experiments. This behavior fits well with
the transfer of a positive charge density, which is due to an
acidic proton that moves from the amine base to the aromatic
part going from D2O/CD3OD to CDCl3 solution. This internal
switch of acidic protons from one part of the molecule to
another could be used in molecular recognition to adapt the
receptor by changing the polarity of the solvent, as well as to
transport information by modulating the environment.[27]
the UV/Vis measurements, in which the involvement of the
chromophores was not detected, indicating that the deproto-
nation must occur on the macrocyclic base.
The last deprotonation step detected by means of potentio-
metric measurements forms the anionic H-1LÀ species and
occurs up to pH 11. In the formation of this species, the most
relevant changes are due to the signals of C2 and C3, which
again show contrasting behavior, shifting upfield and down-
field, respectively. The most important changes in the
1H NMR spectrum are the upfield shift of H1 and the
downfield shift of H4. This trend could be explained by the
involvement of the amine base in this deprotonation step as
well, which leads to a distribution of charge as depicted in
Molecular dynamics (MD) simulation: Starting from the
results obtained from the UV/Vis and NMR experiments, MD
calculations were performed on the anionic HÀ1LÀ species. In
particular, in solvents with a low dielectric constant the acidic
hydrogen atoms are bonded to three out of four oxygen atoms
of the biphenyl moieties. This implies two different arrange-
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V. Fusi, M. Micheloni et al.
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vacuum the situation is
more complicated and two
possible dispositions (L123
and L234) have comparable
energies.
2) Many hydrogen bonds are
present: as donor and ac-
ceptor atoms they involve
the oxygen atoms of the
biphenolate moieties and
the nitrogen atoms bearing
the biphenol side arms. As
expected, by increasing the
dielectric constant of the
medium the number of hy-
Figure 4. 1H NMR spectra of the HÀ1LÀ species in 50:50 (v/v) CD3OD/D2O solution, or in CDCl3.
drogen bonds decreases. No-
ments; the negatively charged oxygen atom could be con-
nected to either the phenyl group close to or that far from the
cyclen ring (Scheme 4). In the following, these two possible
anions were named L123 and L234, where the three numbers
stand for the protonated oxygen atoms.
tably, no hydrogen bonds were detected between the two
biphenolate moieties, meaning that the two aromatic side
arms appear not to interact with each other. We can thus
suppose that the dense hydrogen-bonding networkstabi-
lizing the three acidic hydrogen atoms of the HÀ1LÀ species
should be confined to each nitrogen atom and to the
corresponding linked aromatic side arm. Given this, the
short interaction between the oxygen atom O4 and the
hydrogen atom bonded to O2 (see Table 2, and Figure 1)
found in the solid-state structure of the complex
[Na(HÀ1L)] ¥ CH3CN could be a consequence of the
coordinated sodium cation, which forces the two biphe-
nolate moieties close to each other, acting as a bridge
between the two aromatic arms.
3) No p p stacking interactions were found, confirming the
idea that the biphenolate moieties act separately.
Alkali metal ion complexation: The coordination charac-
‡
‡
‡
teristics of L towards the alkali metal ions Li , Na , K , and
Cs were studied in 0.15 moldmÀ3 NMe4Cl, ethanol/water
‡
50:50 (v/v) solution as mixed solvent at 298.1 K. The stability
constants for the equilibrium reactions of L were determined
potentiometrically and are reported in Table 4. L forms only
Scheme 4. Location of the acidic hydrogen atoms in the species studied by
MD. * denotes that the third hydrogen is bound to N1.
Table 4. Logarithms of the equilibrium constants determined in 50:50
(v/v) H2O/EtOH (0.15 moldmÀ3 NMe4Cl) at 298.1 K for the complexation
reactions of L with Li , Na , K , and Cs ions.
In solvents with high dielectric constants, the three acidic
hydrogens are localized on a nitrogen atom bearing the
biphenol (Scheme 3) and on two oxygen atoms; as a
consequence six different anions result. As above, the
resulting anions are named with the letter L and two numbers
referring to the two protonated oxygen atoms (L12, L13, L14,
L23, L24, and L34, see Scheme 4).
‡
‡
‡
‡
‡
‡
‡
‡
Li
Na
K
Cs
Reaction
‡
HÀ1LÀ ‡ M ! [MHÀ1L]
3.92
3.54
3.29
3.53
mononuclear species with [MHÀ1L] stoichiometry with all
four of the ions examined. The addition constants of the metal
to the HÀ1LÀ species are almost the same for the four metals,
resulting in a log K value of about 3.5 logarithmic units for
each addition constant. Taking into account that the macro-
cyclic base does not bind alkali metal ions under these
experimental conditions, the binding capabilities of L togeth-
er with the absence of selectivity towards these alkali ions
must be attributed to the high adaptability of the side arms to
coordination, which permits binding of the metals but does
not discriminate among them. In other words, considering that
When the dielectric constant was set to 1 and 4.8, only the
anions L123 and L234 where investigated. On the other hand,
for e ˆ 52.5 and e ˆ 80, MD simulations were performed on
L12, L13, L14, L23, L24, and L34. For every MD run only the
conformations within 10 kcalmolÀ1 of the energy minimum
were analyzed. Results are summarized below:
1) Concerning the position of the acidic hydrogen atoms in
the anion studied, it has been found that in polar solvents
the protonation hydrogen-atom distribution proposed as a
result of the UV/Vis and NMR experiments gives rise to
the most stable species (L23). In apolar solvent and in
806
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Chem. Eur. J. 2003, 9, No. 3

Molecular Switches
800 810
coordination in these cases is essentially due to electrostatic
forces, it is possible to suppose that the side arms are
preorganized by the macrocyclic skeleton to coordinate the
metal ions and that they easily adapt around the metals. It is
noteworthy that coordination occurs only with the mono-
anionic species, forming neutral complexes. These species are
also soluble in organic solvents with lower dielectric constants
than the mixed solvent used for the potentiometric measure-
ments.
Interestingly, L can stabilize the metal ions essentially in
two binding areas. One is formed by the tetraamine base and
by two oxygen atoms of the two linked biphenol groups that
are closer to the macrocyclic base; the other one is formed by
the four oxygen atoms of the biphenol chromophores. To
identify the active binding area
lower polarity, for example CH2Cl2 or CHCl3, showed that the
complexation of sodium ion does not influence the chromo-
phores of L, and that the spectra essentially preserve the same
profile for the two species. Given the distribution of the acidic
protons in these solvents, as discussed above, it is possible that
in these solvents the sodium ion is lodged and stabilized by the
four amine functions of the macrocyclic base and by the two
oxygen atoms of the two closer phenol groups in an arrange-
ment similar to that found in the crystal structure of the
sodium complex obtained from CH2Cl2 as solvent.
1
This hypothesis was also confirmed by H and 13C NMR
experiments. For example, Figure 6, which shows the two
spectra of the [NaHÀ1L] species recorded in CDCl3 or
in the mixed solvent D2O/CD3OD 50:50 (v/v), highlights
for the alkali metal ions in sol-
ution and to determine if
a
change of solvent produces a
change in the active binding area,
UV/Vis and NMR spectra of the
[MHÀ1L] species were obtained
and compared with those of the
HÀ1LÀ species recorded under the
same experimental conditions.
The mixed solvent used for the
potentiometric
measurements
and solvents having lower dielec-
tric constant were investigated.
No marked differences in ab-
sorbance or in lmax were found
between the spectrum of L re-
corded at pH 13 in H2O/EtOH,
Figure 6. 13C NMR spectra of the [NaHÀ1L] complex in 50:50 (v/v) CD3OD/D2O, or in CDCl3 solution.
where the HÀ1LÀ is prevalent in solution, with that recorded at
the different distribution of positive charges present
in the two solvents. In particular, in CDCl3 the biphenol
groups show the presence of more intact phenol groups
than in the mixed solvent D2O/CD3OD (C6, C12 shift
upfield in CDCl3), while the amine base is richer in positive
charge in D2O/CD3OD (C4 shift upfield in D2O/CD3OD).
The UV/Vis and NMR experiments performed in water
or in pure alcohol solvent revealed the same behaviors and
‡
pH 13 in the presence of ten equivalents of Na ion to
completely form the [NaHÀ1L] complex. This indicates that
the complexation of sodium does not perturb the optical
properties of the chromophores. Because at least one amine
function in the HÀ1LÀ species bears a positive charge, the
sodium cation cannot be stabilized in that area. The binding
area in this mixed polar solvent must thus be formed by the
four phenol oxygen atoms, in which there is a high density of
negative charges, resulting in an arrangement similar to that
depicted in Figure 5a. This hypothesis was confirmed by the
1H NMR spectrum of the sodium complex, in which the peaks
of the complex in the aromatic region are perturbed in
comparison with those in the spectrum of the HÀ1LÀ species,
while there are no substantial differences between the
aliphatic regions in the two spectra. Comparison of the
spectra of the HÀ1LÀ and [NaHÀ1L] species in solvents with
‡
‡
also gave similar results with the complexes of Li , K , and
‡
Cs .
In conclusion, in solvents with high dielectric constants,
such as water, alcohol, or their mixtures, the binding area is
formed by the oxygen atoms of the biphenol moieties, which
are probably preorganized for coordination by a hydrogen-
bonding networkinvolving the amine base. In contrast, in
solvents with lower dielectric constants, such as CH2Cl2 and
CHCl3, the metal switches to another binding area formed by
the four amine functions of the macrocyclic base and by two
oxygen atoms of the two closer phenol functions. Also in this
case, a hydrogen-bonding networkcan be supposed to
preorganize the side arms. L thus shows the attractive
property of allowing switching of a metal ion inside it, moving
the metal from one part of the molecule to the other by simply
changing the dielectric constants of the solvent (Figure 5a and
5b). Again, as in the case of the above proton switch, this
mode of complexation opens a route for carrying information
using very simple molecules.
Figure 5. Proposed coordination models of alkali ions in [MHÀ1L] species
in a) polar solvents, b) apolar solvents.
Chem. Eur. J. 2003, 9, No. 3
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807

V. Fusi, M. Micheloni et al.
FULL PAPER
afford a brownish oil. The crude product was chromatographed on silica gel
with hexane/ethyl acetate 95:5 as eluent, affording 2 as a white solid (7.83 g,
49%). M.p. 98 1008C; 1H NMR (CDCl3): d ˆ 2.36 (s, 3H), 3.42 (s, 3H),
Conclusion
The molecular topology of ligand L is characterized by the a
tetraamine macrocyclic skeleton on which two 1,1'-bis(2-
phenol) moieties were attached as side-arms. L does not lose
three of its acidic protons in ethanol/water 50:50 (v/v)
solution, probably because of the strong intramolecular
hydrogen-bonding networkin which they are involved. The
disposition of the acidic protons in the several species
produces separation of negative and positive charges in the
ligand in ethanol/water solution. Moreover the acidic protons
in the neutral and anionic HÀ1LÀ species show different
disposition in solvents with high dielectric constants, such as
water or ethanol, than in solvents having lower polarity, such
as CHCl3. At least one proton switches from the macrocyclic
base towards the aromatic side arms on decreasing the
polarity of the solvent. For this reason, this internal proton
switch cannnot only be used as receptor for substrates with an
internal separation of charge, but can also be adapted to the
substrate in molecular recognition by modulation of the
polarity of the medium.
L binds one alkali metal ion in alcohol/water 50:50 (v/v)
solution and in organic solvents. The ligand does not show
selectivity towards the metal ions, but the neutral complexes
obtained are soluble in organic solvents; thus L could be used
to extract such metal ions from their aqueous solution. The
experiments performed suggest that the metal can move
within the complex, switching from a coordination area
formed by the four oxygen atoms of the biphenol moieties
in polar solvents to an area formed by the tetraamine
functions and by two oxygen atoms of the two closer phenol
functions in apolar solvents. This effect, as in the case of the
above proton switch, opens the way to carrying information
using a very simple molecule.
‡
3.81 (s, 3H), 7.2 ppm (m, 7H); MS (ESI): m/z: 229 [M ‡ H] ; elemental
analysis calcd (%) for C15H16O2: C 78.92, H 7.06, N 0.00; found: C 79.0, H
7.1, N 0.0.
3-Bromomethyl-2,2'-dimethoxybiphenyl (3): 3-Methyl-2,2'-dimethoxybi-
phenyl (2) (4.6 g, 0.02 mol), N-bromosuccinimide (3.9 g, 0.022 mol), and
azobisisobutyronitrile (AIBN) (80 mg, 0.5 mmol) were dissolved in CCl4
(40 mL). The resulting mixture was refluxed for 24 h. The mixture was
cooled to room temperature and the solid N-succinimmide was filtered off.
The organic solution was dried over anhydrous Na2SO4 and evaporated to
dryness to afford a yellowish oil. The crude product was recrystallized from
hot methanol, to afford 3 as a white solid (4.9 g, 80%). M.p. 156 1588C;
1H NMR (CDCl3): d ˆ 3.48 (s, 3H), 3.81 (s, 3H), 4.65 (s, 2H), 7.2 ppm (m,
‡
7H); MS (ESI): m/z: 307 309 [M ‡ H] ; elemental analysis calcd for
C15H15BrO2: C 58.65, H 4.92, N 0.00; found: C 58.8, H 5.0, N 0.0.
1,7-Bis[(2,2'-dimethoxybiphen-3-yl)methyl]-4,10-dimethyl-1,4,7,10-tetraaza-
cyclododecane (5): Amine 4 (1 g, 5 mmol) and Na2CO3 (0.5 g, 47 mmol)
were suspended in refluxing CH3CN (100 mL). To this mixture, a solution
of 3 (3.07 g, 10 mmol) in CH3CN (50 mL) was added dropwise over 1 h,
after which the suspension was refluxed for 20 h and then filtered. The
solution was evaporated under vacuum to yield the crude product, which
was chromatographed on neutral alumina (CHCl3/CH3OH 10:0.2). The
eluted fractions were collected and evaporated to yield 5 as a white solid
(2.58 g, 79%). M.p. 55 588C; 1H NMR (D2O, pH 3): d ˆ 2.49 (s, 6H), 2.79
(brs, 8H), 3.01 (brs, 8H), 3.34 (s, 6H), 3.73 (s, 4H), 3.76 (s, 6H), 7.36 (m,
8H), 6.97 ppm (m, 6H); 13C NMR: d ˆ 43.3, 50.0, 52.9, 55.4, 56.7, 62.6,
113.0, 122.0, 126.2, 127.5, 131.2, 132.0, 133.7, 134.9, 157.3, 157.6 ppm; MS
‡
(ESI): m/z: 654 [M ‡ H ]; elemental analysis calcd for C40H52N4O4: C
73.59, H 8.03, N 8.58; found: C 73.4, H 8.1, N 8.5.
1,7-Bis[(2,2'-dihydroxy-biphen-3-yl)methyl]-4,10-dimethyl-1,4,7,10-tetraaza-
cyclododecane tetrahydrobromide (L ¥ 4HBr): Macrocycle
5 (2.0 g,
3 mmol) and phenol (9.0 g, 96 mmol) were dissolved in HBr/CH3COOH
(33%, 80 mL). The solution was stirred at 908C for 22 h. The resulting
suspension was filtered and washed with CH2Cl2 several times. The white
solid obtained was recrystallized from the CH3CN/CH3OH mixture to give
L as its tetrahydrobromide salt (1.3 g, 46%). 1H NMR (D2O, pH 3, 258C):
d ˆ 2.64 (s, 6H), 3.05 (brs, 8H), 3.42 (brs, 8H), 3.72 (s, 4H), 7.14 (m, 8H),
7.36 ppm (t, 6H); 13C NMR d ˆ 42.4, 48.0, 52.2, 54.3, 117.1, 122.7, 124.5,
125.6, 128.4, 131.4, 133.1, 133.3, 153.0, 153.9 ppm; analysis calcd for
C36H48Br4N4O4: C 46.98, H 5.26, N 6.09; found: C 47.1, H 5.4, N 6.2.
The neutral species L can easily be obtained in high yield by treating a
methanol solution of L ¥ 4HBr with a solution of NMe4OH (1.0 moldmÀ3
)
Experimental Section
up to pH 11. Water was added to this solution to complete precipitation of
L as a white solid. M.p. 1868C (decomp); 1H NMR (CDCl3, 258C): d ˆ 2.09
(s, 6H), 2.61 (brs, 8H), 2.80 (brs, 8H), 3.76 (s, 4H), 6.90 (dd, 2H), 7.02 (m,
6H), 7.34 ppm (m, 6H); 13C NMR d ˆ 42.2, 51.6, 55.4, 58.91, 118.5, 119.4,
120.3, 122.6, 127.4, 128.6, 128.7, 131.2, 131.7, 154.8, 155.2 ppm; MS (ESI):
General: Ligand
reported in Scheme 1. 2,2'-Dimethoxydiphenyl (1) and 1,4,7,10-tetrazacy-
clododecane (4) were prepared as previously described.[28, 29] 1H and
L was obtained following the synthetic procedure
.
13C NMR spectra were recorded on a Bruker AC-200 instrument, operating
at 200.13 and 50.33 MHz, respectively. For the 1H NMR experiment, the
peakpositions are reported with respect to HOD ( d ˆ 4.75 ppm); dioxane
was used as the reference standard in 13C NMR spectra (d ˆ 67.4 ppm) that
were obtained in aqueous solution. For the spectra recorded in CDCl3 and
CD3OD, the peakpositions are reported with respect to TMS. 1H 1H and
1H 13C correlation experiments were performed to assign the signals. IR
spectra were recorded on a Shimadzu FTIR-8300 spectrometer. UV/Vis
‡
m/z: 598 [M ‡ H ]; elemental analysis calcd for C36H44N4O4: C 72.46, H
7.43, N 9.39; found: C 72.6, H 7.3, N 9.5.
[Na(HÀ1L)] ¥ CH3CN (6): An excess of NaCl was added to a solution of
L ¥ 4HBr (179 mg, 0.3 mmol) in water (100 mL); NaOH (1 moldmÀ3) was
added until precipitation of a white solid was complete. The solid was then
suspended in CHCl3 (40 mL) and the mixture filtered. The liquid portion
was dried over Na2SO4 and evaporated to dryness. The solid was recrystal-
lized by slow evaporation of a mixture of CH2Cl2/CH3CN, to give white
crystals suitable for X-ray analysis, yield 135 mg (68%). 1H NMR (CD3OD,
258C): d ˆ 1.98 (s, 6H), 2.27 (brs, 4H), 2.51 (brs, 12H), 3.62 (s, 4H), 6.69 (t,
4H), 6.81 (d, 2H), 6.93 (d, 2H), 7.09 (t, 2H), 7.30 ppm (d, 4H); 13C NMR:
d ˆ 43.3, 51.6, 55.0, 56.4, 118.0, 119.4, 120.9, 127.8, 129.4, 131.2, 131.8, 131.9,
132.6, 159.3, 162.9 ppm; elemental analysis calcd for C38H46N5NaO4: C
69.17, H 7.03, N 10.61; found: C 69.2, H 7.1, N 10.5.
absorption spectra were recorded at 298 K on
a Varian Cary-100
spectrophotometer equipped with a temperature control unit. ESI mass
spectra were recorded on a ThermoQuest LCQ Duo LC/MS/MS spec-
trometer. Melting points were determined on a B¸chi B-540 apparatus.
Solvents and starting materials were used as purchased.
3-Methyl-2,2'-dimethoxybiphenyl (2): A solution of butyllithium (21 mL,
10m in THF) was added to 2,2'-dimethoxybiphenyl (1) (15.0 g, 0,07 mol)
dissolved in freshly distilled THF (500 mL). The addition of butyllithium
caused vigorous refluxing. The resulting solution was stirred for 30 min and
a solution of dimethyl sulfate (26.5 g, 0.21 mol) dissolved in freshly distilled
THF (50 mL) was then added dropwise. The addition of dimethyl sulfate
caused vigorous refluxing. Excess dimethyl sulfate was destroyed by
stirring the organic layer with 1m NaOH (400 mL). The organic solution
was separated, dried over anhydrous Na2SO4, and evaporated to dryness to
Caution: Perchlorate salts of organic compounds are potentially explosive;
these compounds must be prepared and handled with great care!
X-ray crystallographic studies on [Na(HÀ1L)] ¥ CH3CN (6): For crystal
structure determination, cell parameters and intensity data for compound 6
were obtained on a Siemens P4 diffractometer, using graphite-monochro-
mated CuKa radiation (l ˆ 1.54184 ä). Cell parameters were determined by
least-squares fitting of 25 centered reflections. The intensities of three
808
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Chem. Eur. J. 2003, 9, No. 3

Molecular Switches
800 810
standard reflections were periodically measured to checkthe stability of
the diffractometer and the decay of the crystal. Intensity data were
corrected for Lorentz and polarization effects and an absorption correction
was applied once the structure was solved by the method of Walker and
Stuart.[30] The structure was solved by using the SIR-97[31] program and
subsequently refined by the full-matrix least-squares program SHELX-
97.[32] The hydrogen atoms bonded to the oxygen atoms O1, O2, and O3
were found in difference syntheses and their positions and isotropic
displacement parameters were refined. All of the other hydrogen atoms
were introduced in calculated positions and their coordinates refined in
agreement with that of the linked atoms. All of the non-hydrogen atoms
were refined anisotropically. Atomic scattering factors and anomalous
dispersion corrections for all the atoms were taken from reference [33].
Geometric calculations were performed by PARST97.[34] The molecular
plot was produced with the ORTEP-3 program.[35] Crystal and structure
refinement data are reported in Table 5.
EMF measurements: Equilibrium constants for protonation and complex-
ation reactions with L were determined by pH-metric measurements
‡
(pH ˆ Àlog [H ]) in 50:50 (v/v) ethanol/water solution at 298.1 Æ 0.1 K
with 0.15 moldmÀ3 Me4NCl as ionic medium, using the fully automatic
equipment that has already been described;[38] the EMF data were acquired
with the PASAT computer program.[39] The combined glass electrode was
calibrated as a hydrogen concentration probe by titrating known amounts
of CO2-free HCl with Me4NOH solutions and determining the equivalent
point by Gran×s method,[40] which gives the standard potential E8 and the
ionic product of water (pKw ˆ 14.53(1) at 298.1 K in 0.15 moldmÀ3 Me4NCl,
‡
Kw ˆ [H ][OHÀ]) for the mixed solvent EtOH/H2O. Ligand and metal ion
concentrations of 1 Â 10À3 3 Â 10À3 were employed in the potentiometric
measurements; we performed at least three measurements in the pH 2 11
range. The HYPERQUAD computer program was used to process the
potentiometric data.[41] All titrations were treated either as single sets or as
separate entities for each system, without significant variation in the values
of the constants determined.
Table 5. Crystal and structure refinement data for compound 6.
Acknowledgement
empirical formula
formula weight
temperature [K]
l [ä]
crystal system
space group
a [ä]
b [ä]
c [ä]
b [8]
V [ä3]
C38H46N5NaO4
659.79
298
1.5418
monoclinic
P21/c
12.805(1)
20.205(3)
14.170(2)
100.77(1)
3601.6(8)
4
¡
Financial support from the Italian Ministero dell'Universita e della Ricerca
Scientifica e Tecnologica (COFIN2000) and CRIST (Centro di cristallog-
rafia strutturale) University of Florence are gratefully acknowledged.
[1] a) C. J. Pedersen, J. Am. Chem. Soc. 1967, 89, 7017; b) D. J. Cram, J. M.
Cram, Science 1984, 183, 4127; c) J.-M. Lehn, Angew. Chem. 1988, 100,
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Tamburini, P. A. Vigato, Coord. Chem. Rev. 1995, 110, 17; e) R. M.
Izatt, K. Pawlak, J. S. Bradshaw, Chem. Rev. 1995, 95, 2529.
[2] a) L.-F. Lindoy, The Chemistry of Macrocyclic Ligand Complexes,
Cambridge University Press, Cambridge, 1989; b) J.-S. Bradshaw,
Aza-crown Macrocycles, Wiley, New York, 1993; c) P. Dietrich, P.
Viout, J.-M. Lehn, Macrocyclic Chemistry, VCH, Weinheim, 1993.
[3] a) N. V. Gerbeleu, V. B. Arion, J. Burgess, Template Synthesis of
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1996.
Z
1calcd [gcmÀ3
]
1.217
0.740
1408
7 120
m [mmÀ1
]
F(000)
2q range for data collection [8]
reflections collected/unique
data/parameters
final R indices [I > 2s(I)]
R indices (all data)
6944/5758 [R(int) ˆ 0.0159]
4905/450
R1 ˆ 0.0430, wR2 ˆ 0.1181
R1 ˆ 0.0508, wR2 ˆ 0.1260
[4] G. W. Gokel, Crown Ethers and Cryptands (Monographs in Supra-
molecular Chemistry) (Ed.: J. F. Stoddart), The Royal Society of
Chemistry, Cambridge, 1992.
[5] S. Patai, A. Rapport, E. Weber, Crown Ethers and Analogs, Wiley,
New York, 1998.
[6] H. J. Schneider, A. Yatsimirsky, Principles and Methods in Supra-
molecular Chemistry, Wiley, Chichester, 2000.
[7] A. Bianchi, K. Bowman-James, E. Garcia-Espanƒa, Supramolecular
Chemistry of Anions, Wiley-VCH, Weinheim, 1997.
CCDC-185898 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/
conts/retrieving.html (or from the Cambridge Crystallographic Data
Centre, 12, Union Road, Cambridge CB21EZ, UK; fax: (‡44)1223-336-
033; or deposit@ccdc.cam.ac.uk).
Molecular dynamics (MD) simulation protocol: The species studied was
the [HÀ1L]À ion. The MSI software programs InsightII and Discover
version 98.0 were used for all of the molecular modeling studies.[36] The
force field used was the ESFF because it has the correct atom type for all of
the atoms in the ligand. MD calculations were performed at 300 K and the
Verlet leapfrog algorithm, with a time step of 1 fs, was used for integration
of equations of motion in all simulations. A distance-dependent dielectric
constant was used and set to 1, 4.8, 52.5, and 80 to simulate vacuum,
chloroform, water/ethanol (50/50), and water environments, respectively.
Before starting each MD procedure the initial anionic species was
optimized until the convergence criterion was met (<0.01 kcalmolÀ1).
For every MD run the system was allowed to equilibrate for 100 ps and then
a 1000 ps dynamic study was performed (snapshot conformations were
collected every ps). A conformational search was performed to verify the
possibility for the aromatic rings belonging to different arms to reach
distances compatible with the presence of p p stacking interactions. A set
of four independent dihedral angles was varied: C13-C12-C11-N1, C13-
C14-C18-C19, C26-C25-C24-N3, C26-C27-C31-C32. They were varied in
constant steps of 308 in the 0 3608 range. This search revealed that only the
(C18 C23) and (C31 C36) aromatic rings could have this kind of
interaction, because the shortest distance between the (C12 C17) and
[8] a) A. W. Czarnik, Fluorescent Chemosensors for Ion and Molecule
Recognition, Am. Chem. Soc., Washington DC, 1993; b) R. Bergonzi,
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31.
[9] C. Bazzicalupi, A. Bencini, A. Bianchi, V. Fusi, C. Giorgi, A. Masotti,
F. Pina, A. Roque, B. Valtancoli, J. Chem. Soc. Chem. Commun. 2000,
561 562.
[10] Y. A. Zoltov, Macrocyclic Compounds in Analytical Chemistry, Wiley-
Interscience, New York, 1997 .
[11] a) R. Ballardini, V. Balzani, A. Credi, M. T. Gandolfi, M. Venturi,
Struc. Bond. 2001, 99, 163; b) P. Ashton, R. Ballardini, V. Balzani, A.
Credi, K. R. Dress, E. Ishow, C. J. Kleverlaan, O. Kocian, J. A. Preece,
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