Synthesis and coordination properties of new macrocyclic ligands: Equilibrium studies and crystal structures

Article abstract of DOI:10.1039/b408808e

The synthesis and characterization of two new macrocyclic ligands, the bis-macrocyclic compound 2,6-bis(1,4,13-triaza-7, 10-dioxacyclopentadec-1- ylmethyl)phenol (L) and 38-methoxy-1,4,13,16,19,28-hexaaza-7,10,22,25- tetraoxatricyclo[14.14.7.l ^32,36]octatriconta-32,34, Δ^36'38-triene (L1) are reported. Equilibrium studies of basicity and coordination properties toward metal ions such as Cu(II), Zn(II), Cd(II) and Pb(II) were performed for ligand L by potentiometric measurements in aqueous solution (298.1 ± 0.1 K, I = 0.15 mol dm^-3). L behaves as a hexaprotic base (logK₁, = 10.93, logK₂ = 9.70, logK₃ = 8.79, logK₄ = 8.05, logtK₅ = 6.83, logK₆ = 2.55). All metal ions form stable mono- and dinuclear complexes: log_MLH-1 = 25.61 for Cu(II), 15.37 for Zn(II), 12.58 for Cd(II) and 13.79 for Pb(II); logK_M2LH-1 = 31.61 for Cu(II), 23.38 for Zn(II), 24.49 for Cd(II) and 23.68 for Pb(II). All these dinuclear species show a great tendency to add the OH^- group: the equilibrium constant for the addition reaction was found to be logK_M2LH-1OH = 4.77 for Cu(II), 5.66 for Zn(II), 2.8 for Cd(II) and 3.18 for Pb(II). In the case of Ni(II), kinetic inertness prevents the possibility of solution studies. The dinuclear solid adducts [Ni₂H_-1L(N₃)₃] ·EtOH and [Cu₂H_-1L(N₃)](ClO ₄)₂ were characterized by X-ray analysis.

Full text of DOI:10.1039/b408808e

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F U L L P A P E R
Synthesis and coordination properties of new macrocyclic ligands:
equilibrium studies and crystal structures
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 Pontellinia and Patrizia Rossib
a
Institute of Chemical Sciences, University of Urbino, P.zza Rinascimento 6, I-61029, Urbino,
Italy. E-mail: mauro@uniurb.it; Fax: +39-0722-350032; Tel: +39-0722-350032
Department of Energy Engineering, University of Florence, via S. Marta 3, I-50139, Florence,
b
Italy
Received 10th June 2004, Accepted 2nd September 2004
First published as an Advance Article on the web 17th September 2004
The synthesis and characterization of two new macrocyclic ligands, the bis-macrocyclic compound 2,6-bis(1,4,13-
triaza-7,10-dioxacyclopentadec-1-ylmethyl)phenol (L) and 38-methoxy-1,4,13,16,19,28-hexaaza-7,10,22,25-
tetraoxatricyclo[14.14.7.132,36]octatriconta-32,34,D36,38-triene (L1) are reported. Equilibrium studies of basicity and
coordination properties toward metal ions such as Cu(II), Zn(II), Cd(II) and Pb(II) were performed for ligand L by
potentiometric measurements in aqueous solution (298.1 ± 0.1 K, I = 0.15 mol dm−3). L behaves as a hexaprotic
base (logK1 = 10.93, logK2 = 9.70, logK3 = 8.79, logK4 = 8.05, logK5 = 6.83, logK6 = 2.55). All metal ions form
stable mono- and dinuclear complexes: logKMLH = 25.61 for Cu(II), 15.37 for Zn(II), 12.58 for Cd(II) and 13.79
−1
for Pb(II); logKM LH = 31.61 for Cu(II), 23.38 for Zn(II), 24.49 for Cd(II) and 23.68 for Pb(II). All these dinuclear
2
−1
species show a great tendency to add the OH− group: the equilibrium constant for the addition reaction was
found to be logKM LH OH = 4.77 for Cu(II), 5.66 for Zn(II), 2.8 for Cd(II) and 3.18 for Pb(II). In the case of Ni(II),
2
−1
kinetic inertness prevents the possibility of solution studies. The dinuclear solid adducts [Ni2H−1L(N3)3]·EtOH and
[Cu2H−1L(N3)](ClO4)2 were characterized by X-ray analysis.
Introduction
The chemistry research community has always shown great
interest in transition dinuclear metal complexes and ligands
capable of yielding them due to the key role they play in many
synthetic and biological applications. In fact, dinuclear metal
complexes have been used successfully for the recognition and
assembly of external species of different nature, including
inorganic and organic substrates.1–5 Many hydrolytic metallo-
enzymes contain two divalent transition metal ions in close
proximity which together form their active site.6–9 For example,
urease catalyzes the hydrolysis of urea and small amine
substrates around a dinuclear Ni(II) center,10 while alkaline
phosphatase has Zn(II) as divalent ion,11 and tyrosinase is a
monooxygenase enzyme that has a dinuclear copper active site
and is responsible for the hydroxylation of substrates.12 In these
systems, the distance between the two metals is crucial to allow
the cooperation of both metal ions in the active center: for exam-
ple, in hemocyanins 3.7 Å is the distance between the two copper
ions necessary to allow binding and transport of dioxygen in
the hemolymph of mollusks.13 Recently, we published results on
transition dinuclear metal complexes formed with the ligand L2
which are able to bind small molecules such as dioxygen, nitric
oxide and others14 (see Scheme 1). These dinuclear complexes
are characterized by metals close to each other and thus able
to cooperate and bind a new species which is coordinated in
a bridged disposition between the two metal centers. With the
Scheme 1 Schematic drawings of L, L1 and L2 ligands.
aim of synthesizing ligands able to bind two transition metal
ions, we have now synthesized a new macrocyclic ligand 2,6-
bis(1,4,13-triaza-7,10-dioxacyclopentadec-1-ylmethyl)phenol
(hereafter abbreviated as (L)) showing two macrocyclic sub-
units ([15]aneN3O2) spaced by a phenolic function and preserv-
ing the same binding skeleton as L2. This synthesis led to the
isolation and characterization of L1 (see Scheme 1), an isomeric
ligand of L obtained in a very low yield. Ligand L can bind
transition metal ions, forming dinuclear complexes in which the
two metals are in close proximity. The two coordinated metals
show an unsaturated coordination environment and thus can be
used as receptors for secondary ligands.
Results and discussion
Ligand preparation
Fig. 1 reports the synthetic pathway used to obtain compound
2,6-bis(1,4,13-triaza-7,10-dioxacyclopentadec-1-ylmethyl)-
phenol (L) and 38-methoxy-1,4,13,16,19,28-hexaaza-7,10,22,25-
tetraoxatricyclo[14.14.7.132,36]octatriconta-32,34,D36,38-triene
(L1). The scheme also provides the previous synthesis pathway
for the tetratosylated compound 2, which was synthesized in
good yield by reacting 1 with tosyl chloride in chloroform in
3 4 6 8
D a l t o n T r a n s . , 2 0 0 4 , 3 4 6 8 – 3 4 7 4
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

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Table 1 Protonation constants (logK) of L in H2O at 298.15 K, I =
the presence of a base. Compound 2 is a versatile building block
that can be used to structure the coordination pattern of L2.
In fact, starting from 2, it is possible to link its four tosylamide
groups by means of a cyclization reaction and thus produce
different macrocyclic ligands. The properties of the ligands
obtained can be varied by choosing suitable reactants. In this
case, a derivative of a simple polyethylene glycol (3) was chosen
as cyclization reagent. Although many other phenolic bridged
ligands have been reported, the aim of the present work was
to stiffen the molecular skeleton of L2 without inserting other
strong binding groups. Moreover, given the several binding
sites in 2, we wanted to determine the most favourable closing
cyclization of 2 using a short and flexible reactant. In fact, in
the most critical cyclization step (see Fig. 1) two main products
are formed (4 and 5): the main compound (5) is obtained in
25% yield with the following two cyclizations, one involving
the two tosyl amide groups of one of the triamine subunits
and one on the other triamine subunit, forming two separate
fifteen-membered [15]aneN3O2 macrocycles. Product 4, which
gave a significant lower yield (5%), arises from two cycliza-
tion reactions which link two tosylamide groups belonging to
different triamine subunits. This new compound is formed by a
single large thirty-membered [30]aneN6O4 macrocycle with two
opposite nitrogen atoms bridged by the phenolic group and can
thus be considered a large cryptand.
0.15 mol dm−3 NaCl
Reaction
logK
H−1L− + H+ = L
10.93(1)a
9.70(1)
8.79(2)
8.05(1)
6.83(1)
2.55(2)
L + H+ = LH+
LH+ + H+ = LH22+
LH22+ + H+ = LH33+
LH33+ + H+ = LH44+
LH44+ + H+ = LH55+
a Values in parentheses are the standard deviations on the last significant
figure.
all the aromatic groups. A similar procedure carried out with 5
led to the fifteen-membered [15]aneN3O2 macrocycle.
Equilibrium studies
Basicity. Table 1 summarizes the basicity constants of L as
potentiometrically determined in 0.15 mol dm−3 NaCl aqueous
solution at 298.1 K. Under the experimental conditions used,
the neutral compound L behaves as monoprotic acid and as a
pentaprotic base, although it has a total seven protonation sites.
As shown in Table 1, L can be present in solution as anionic
species H−1L−, and the stepwise basicity constants are reported
starting from this species. The sequence of basicity constants of
L can be easily explained in terms of positive charge repulsions.
It is interesting to compare the basicity behavior of L with that
of the related non-cyclic molecule 2,6-bis([bis(2-aminoethyl)-
amino]methyl}phenol L2.14a The latter molecule cannot be com-
pletely deprotonated under the usual experimental conditions
because it is too strong base. Spectroscopic studies allowed the
explanation of this basicity strength in terms of charge delocal-
ization among phenolic oxygen and nitrogen atoms present in
the lateral chains. In L the lateral chains containing the nitrogen
atoms are portions of two macrocyclic frames of [15]aneN3O2;
thus, the primary nitrogen atoms become secondary and the
overall molecular framework less flexible; these conditions of
reduced flexibility and the different set of donor atoms make L
less basic than L2.
Coordination of metal ions. Table 2 reports the formation
constants of different metal ions as potentiometrically
determined in 0.15 mol dm−3 NaCl aqueous solution at 298.1 K.
The symmetric molecular topology of L with two macrocyclic
subunits linked by phenolic group is ideal for the formation of
dinuclear complexes: L forms stable dinuclear complexes with
all of the metal ions investigated, with the phenolate group
bridging the two metal ions, and allows them to be close to each
other in a coordination environment which is still unsaturated.
Indeed, for Cu(II), Zn(II) and Pb(II) the dinuclear species
M2H−1L3+ shows a great tendency to add the OH− group and
form dinuclear hydroxo species such as [M2H−1L(OH)]2+. The
involvement of the phenolate oxygen atom in the stabilization
via a bridging disposition of both metal ions was confirmed
by UV-Vis studies in the case of the L/Cu(II) system. The UV
electronic spectrum, recorded in aqueous solution at the pH
value where the [Cu2(H−1L)]3+ species is prevalent in solution,
shows four principal bands: kmax 242 (sharp, e = 11200), 276
(sharp, e = 8400), 374 (sharp, e = 450) and 710 nm (large,
ε = 200 dm3 cm−1 mol−1). The two bands at higher energy are due
to the p–p* transitions of the phenolate group engaged in the
coordination of the metals;15 the band at 374 nm can be ascribed
to the phenolate–copper charge transfer when the oxygen atom
bridges two Cu(II) ions,15 while the large band with kmax 710 nm is
due to the d–d electron transfer of the metal. These data indicate
the involvement of the oxygen of the aromatic chromophore as
phenolate in the stabilization of the complex and, moreover,
that it bridges the two metals in the dinuclear species. However,
L also forms mononuclear species with the four M(II) ions
Fig. 1 Synthetic pathway used to obtain compounds L and L1.
The final ligands L and L1 were obtained by simultaneous
deprotection of the four tosyl and one methyl phenolic groups
in lithium–liquid ammonia, following a standard procedure.
The overall yields for the synthesis of L and L1 were 17 and
1
3%, respectively. Compounds L and L1 gave similar H and
13C NMR spectra showing the same symmetry mediated on
the NMR time scale and elemental analyses gave identical
results; thus, the attribution of their molecular structure was
very complicated. In the case of L this was done by solving
the crystal structure, while for L1 the molecular structure was
inferred as shown in Scheme 1.
This structure was attributed taking into account the possible
cyclization and above all the ESI mass spectra which showed the
same molecular peak for both compounds. The molecular struc-
ture of L1 was also validated by the product obtained following
a standard deprotection of the tosyl groups with an HBr–AcOH
mixture.14a In this case, the main product obtained was the thirty-
membered [30]aneN6O4 macrocycle derived from 4 by removing
D a l t o n T r a n s . , 2 0 0 4 , 3 4 6 8 – 3 4 7 4
3 4 6 9

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Table 2 Formation constants (logK) of L with Cu(II), Zn(II), Cd(II) and Pb(II) ions in H2O at 298.15 K, I = 0.15 mol dm−3 NaCl
Reaction
M = Cu
M = Zn
M = Cd
M = Pb
M2+ + H−1L− = MH−1L+
M2+ + L = ML2+
25.61(2)a
21.17(1)
6.84(1)
4.35(1)
3.65(2)
3.55(1)
3.07(1)
6.00(1)
4.77(3)
—
15.37(1)
13.53(1)
9.44(2)
8.45(1)
—
—
—
8.01(1)
5.66(3)
2.72(2)
12.58(1)
11.16(1)
9.85(2)
8.37(1)
—
—
—
11.91(1)
2.8(1)
—
13.79(1)
11.49(1)
9.32(1)
8.43(2)
—
—
—
9.89(1)
3.18(2)
—
MH−1L+ + H+ = ML2+
ML2+ + H+ = MHL3+
MHL3+ + H+ = MH2L4+
MH2L4+ + H+ = MH3L5+
MH−1L+ + OH− = MH−1L(OH)
MH−1L+ + M2+ = M2H−1L3+
M2H−1
M2H−1L(OH)2+ + OH− = M2H−1L(OH)2+
L
3+ + OH− = M2H−1L(OH)2+
a Values in parentheses are the standard deviations on the last significant figure.
examined. The binding constant for the Cu(II) complex is very
large: 21.17 log units, as reported in Table 2. This value is however
comparable with the binding constant for the related macrocycle
[15]aneN3O2: logK = 15.51 as already reported.16 The difference
can be explained by taking into consideration that in the case of
L there is one extra phenolic oxygen as donor atom. The mono-
nuclear species are the most prevalent in solution when using a
ligand:metal molar ratio of 1:1; when the L/M(II) molar ratio
is lower, dinuclear species become prevalent and are almost the
only species present in solution at a ligand:metal molar ratio
of 1:2. This behavior is depicted, for example, in Fig. 2(a) and
(b), which show the distribution diagrams for these species for
the system L/Zn(II), at 1:1 and 1:2 molar ratios respectively,
as a function of pH. All of the [MH−1L]+ mononuclear species
undergo at least two easy protonations, suggesting, as in the case
of L2, that only one macrocyclic subunit is strongly involved
in the coordination of a M(II) ion while the other unit remains
available for protonation.
Upon comparison of the stability of the complexes formed
with L and L2, it is possible to note that the Cu(II) and Zn(II)
complexes formed with L are significantly less stable than those
found with L214a,d (see Table 2). This clearly indicates that the
presence of the bulky oxygen containing macrocycles makes
the overall molecular framework less flexible and adaptable to
the metal ion coordination requirement; moreover, the oxygen
atoms introduced do not participate in stabilizing the metal ions.
On the contrary, the Pb(II) dinuclear complexes show a signifi-
cantly higher stability, leading us to suppose that in the case of
harder metal ions, the oxygen atoms of the [15]aneN3O2 subunits
contribute to stabilize the species.
X-Ray crystal structures
In [Ni2(H−1L)(N3)3]·EtOH (6) the asymmetric unit contains
half of the dinuclear complex, one and a half azide anions and
a disordered molecule of ethanol to which a population para-
meter of 0.5 was assigned. The two halves of the metal complex
are related by a two-fold symmetry axis which passes through an
azide anion, namely N(7)–N(8)–N(9) and the O(1), C(1), C(4)
and H(4) atoms of the ligand (Fig. 3). In the crystal structure
of [Cu2(H−1L)(N3)](ClO4)2 (7) the asymmetric unit is made up
of one molecule of the dinuclear complex, an azide ion and two
perchlorate anions (Fig. 4).
Fig. 3 ORTEP view of the dinuclear Ni(II) complex 6. For the sake
of clarity only the independent atoms have been labelled. Ellipsoids are
drawn at 30% probability.
The way in which the H−1L− species is wrapped around the
metal ions filling, albeit only partially, their coordination sites
is almost identical in both the metal complexes, i.e. it provides
four donor atoms for each cation, namely N(1), N(2), N(3) and
Fig. 2 Distribution diagrams of the species for the system L/Zn(II)
as a function of pH in aqueous solution, I = 0.15 mol dm−3 NaCl,
at 298.1 K. (a) [L] = 1 × 10−3 mol dm−3, [Zn2+] = 1 × 10−3 mol dm−3;
(b) [L] = 1 × 10−3 mol dm−3, [Zn2+] = 2 × 10−3 mol dm−3.
3 4 7 0
D a l t o n T r a n s . , 2 0 0 4 , 3 4 6 8 – 3 4 7 4

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In both the metal complexes the geometrical parameters of the
azide anions are within the expected range.
Given that the [15]aneN3O2 macrocycle acts as a tridentate
ligand through the nitrogen atoms, its binding skeleton strongly
resembles that of L2. This similarity prompted us to compare
the 3D arrangement of the phenol group and the polyamine
side arms of L, as found in 6 and 7, with the corresponding
atoms of L2 in the dinuclear complexes of Ni(II) and Cu(II),
already reported14a (hereafter denoted as Ni2L2 and Cu2L2),
and the latter metal ions were found to show a coordination
environment that is very similar to that of the current complexes.
The relative arrangement of the mean planes described by the
equatorial donors and the phenol ring in 6, 7, Ni2L2 and Cu2L2
is also quite similar. The pronounced binding similarity between
L and L2 is also provided by the root mean square values
obtained from the superimposition (Fig. 5) of the non-hydrogen
atoms of the phenol group and the polyamine side arms: 0.46 for
the 6/Ni2L2 couple and 0.57 for the 7/Cu2L2 pair.
Fig. 4 ORTEP view of the dinuclear Cu(II) complex 7. Ellipsoids are
drawn at 30% probability.
the phenyl oxygen atom O(1). In both structures the latter acts
as bridging unit between the two metal ions, keeping the Ni(II)
and the Cu(II) ions in close proximity (3.150(7) and 3.118(3) Å,
respectively). The restricted number of donors (four) supplied
by the ligand to each metal ion and the closeness of the two
metal cations enable the latter to assemble and share external
species in order to complete their coordination sphere, as already
reported on ligands featuring a coordination pattern similar to
that provided by L. In those cases the two metal ions worked
together to recognize external guests such as chloride, hydroxide,
azide, and butanolate anions.14a–c In the present paper the M–M
distances, which are in the expected range for Ni(II) and Cu(II)
binuclear complexes featuring analogous bridging units,17 well
suit the recognition and the assembly of the azide anion, in
which the nitrogen atom N(7) further links the two metal ions.
In the crystal structure of 6 each nickel ion completes its
coordination sphere, which can be described as an elongated
octahedron, thanks to N(4) which belongs to another azide
ion. The Ni-donor atom bond distances are in the range usually
observed for analogous Ni(II) complexes as provided by a search
in the Cambridge Structural Database (CSD) v. 5.25,17 with the
Ni(1)–N(3) (2.164(2) Å) and Ni(1)–N(4) (2.168(3) Å) distances
significantly longer than the Ni–N equatorial bonds (mean
value 2.08 Å). The atoms O(1), N(1), N(2) and N(7) lie well in
a plane and the metal ion is displaced from it only 0.0171(4) Å
towards N(4).
Fig. 5 Binding skeleton superimposition of the 7/Cu2L2 (left) and
6/Ni2L2 (right) couples.
Finally, in both species the macrocycles exhibit a quite
complex conformation resulting from two different types of
interactions. As already stated, while the region of the nitrogen
donors is involved in the coordination of the metal ions, the non-
coordinating oxygen atoms O(2) and O(3) in 6 and O(2), O(3),
and O(4), O(5) in 7 are involved, as acceptors, in several intra-
molecular H-bonds. Particularly in 6, N(2) is hydrogen bonded
to O(2) and O(3); the distances are: 2.900(4) and 2.922(4) Å,
respectively. In 7 the corresponding distances are 2.76(1)
and 2.94(1) Å, and 2.81(1) and 2.97(1) Å for the interactions
between the nitrogen atom N(5) and O(4) and O(5), respec-
tively. Moreover, the nitrogen atom N(3) in 6 interacts with the
symmetry-related N(4) atom reported by the operation −x + 1,
y, −z + 1/2 + 1, the distance being 3.009(3) Å.
Conclusions
In 7, the coordination sphere (vide infra) described by the
ligand and the bridging azide ion around the Cu(II) ions
strictly resembles that of the dinuclear nickel complex 6.
Thus each copper ion has a square pyramidal coordination
geometry (Fig. 4), with the Cu(II) ions slightly shifted towards
the apical donors (the maximum displacement from the mean
plane defining the base being that of Cu(1) (0.274(2) Å). All
the Cu–donor atom distances are in agreement with those of
analogous complexes found in the CSD, with, as expected, the
bond lengths involving the apical donors longer with respect
to the other Cu–N distances. Incidentally, for each Cu(II) ion,
the sixth coordination site of the octahedron appears to be
occupied by a perchlorate oxygen atom, even though the latter
is definitely distant from the metal ions (>3.20 Å). This is also
true for the already reported solid state structure of the copper
binuclear complex with L2 (vide infra).14b The IR spectra show
only asymmetric stretching of the azide at 2079 cm−1 attributed
to the l-1,1-azido bridge between the two metal ions.18
In order to synthesize the new ligands L and L1 we first
synthesized compound 2, a suitable building block show-
ing the coordination environment present in L2. During the
cyclization step, two isomeric ligands L1 and L, obtained in
different yields, were isolated. The two ligands arise from two
different cyclization schemes. L1 is a large cryptand formed by
a thirty-membered [30]aneN6O4 macrocycle with two opposite
nitrogen atoms bridged by the phenolic group, while L contains
two [15]aneN3O2 macrocyclic subunits linked by a 2,6 dimethyl-
phenol unit. The coordination behavior of L towards several
bipositive metal ions was investigated. L forms stable dinuclear
complexes with Cu(II), Zn(II), Cd(II) and Pb(II) ions, in which
the phenolate group bridging the two metal ions allows them to
be close to each other in an unsaturated coordination environ-
ment. Solution studies highlighted the great tendency of the
[M2H−1L]3+ species to bind hydroxide, suggesting that the OH−
probably bridges the two metal centres. Kinetic inertness in the
complex formation of the Ni(II)/L system prevented the evalua-
tion of the stability constants. In any case, the crystal structures
obtained confirm the tendency to add an extra ligand such as
the azide anion to the dinuclear complexes. The coordination
The mean planes described by the equatorial donors in 7 form
an angle of 19.3(3)° each other and of 12.5(3) and 14.6(3)° with
the aromatic ring, respectively. In 6 the four equatorial donors
are almost coplanar with respect to the phenol moiety (8.6(1)°).
D a l t o n T r a n s . , 2 0 0 4 , 3 4 6 8 – 3 4 7 4
3 4 7 1

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features of the dinuclear complexes formed with L will permit
their use in biological mimicking of active bimetallic centres and
in molecular recognition of further substrates.
under vacuum. The crude product was chromatographed on
neutral alumina (CH2Cl2–MeOH, 100:0.2). The eluted fractions
were collected and evaporated, affording 4 (4.5 g, 24%) and 5
(0.9 g, 4.8%) as white solids.
Experimental
General methods
Compound 4. Anal. Calc. for C57H78N6O13S4: C 57.85, H 6.64,
N 7.10. Found: C 57.7, H 6.5, N 7.0%.
1H and 13C NMR spectra were recorded with a Bruker AC-200
instrument, operating at 200.13 and 50.33 MHz, respectively.
Peak positions are reported in relation to TMS (CDCl3) or HOD
at 4.75 ppm (D2O). Dioxane was used as reference standard in
13C NMR spectra (67.4 ppm). IR spectra were recorded with
a Shimadzu FT-IR-8300 spectrometer. UV absorption spectra
were recorded at 298 K with a Varian Cary-100 spectrophoto-
meter equipped with a temperature control unit. ESI mass
1H NMR (CDCl3): d 7.84 (d, 2H), 7.70 (d, 8H), 7.30 (d, 8H),
7.23 (t, 1H), 3.67 (m, 7H), 3.60 (m, 8H), 3.49 (s, 8H), 3.36
(m, 8H), 3,27 (m, 16H), 2.43 (s, 12H).
13C NMR (CDCl3): d 157.4, 143.6, 136.5, 132.6, 129.7, 127.0,
126.9, 123.8, 72.7, 70.5, 61.8, 53.7, 53.4, 49.7, 48.3, 21.5.
Compound 5. Anal. Calc. for C57H78N6O13S4: C 57.85, H 6.64,
N 7.10. Found: C 58.0, H 6.7, N 7.0%.
1H NMR (CDCl3): d 7.64 (d, 2H), 7.49 (d, 8H), 7.26 (t, 1H),
7.15 (d, 8H), 3.67 (s, 4H), 3.74 (s, 3H), 3.59 (m, 8H), 3.53 (s, 8H),
3,26 (m, 16H), 2.63 (m, 8H), 2.31 (s, 12H).
spectra were recorded with
LC/MS/MS spectrometer. All reagents and solvents used were
of analytical grade.
a ThermoQuest LCQ Duo
13C NMR (CDCl3): d 157.3, 143.1, 136.5, 132.6, 129.7, 129.4,
126.9, 123.8, 72.5, 70.5, 61.8, 53.7, 53.4, 49.6, 48.3, 21.4.
Synthesis
The overall synthetic sequence used to obtain compounds L
and L1 is reported in Fig. 1. 2,6-bis{[bis(2-aminoethyl)amino]-
methyl}anisole 1 was prepared as previously described;19
solvents and starting materials were used as purchased.
Compound L·6HBr
Ammonia (300 cm3) was condensed in a suspension of 4 (4.5 g,
3.8 mmol) in diethyl ether (30 cm3) and methanol (1 cm3), cooled
at −70 °C. Small pieces of lithium were added to the mixture until
the suspension turned blue. Thirty minutes after the suspension
turned blue, NH4Cl (12 g, 0.2 mol) was added. The white solid
obtained after the evaporation of the solvents was treated with
3 mol dm−3 HCl (3 × 100 cm3). The acidic solution was filtered
and then evaporated to dryness, after which the resulting solid
was dissolved in the minimum amount of water necessary and
the solution made alkaline with concentrated NaOH. The liquid
was extracted with CHCl3 (6 × 50 cm3). The organic layer was
dried over Na2SO4 and vacuum-evaporated to obtain a solid
that was dissolved in ethanol and treated with 48% HBr until
complete precipitation of a white solid, which was filtered off to
obtain L as a hexahydrobromide salt (2.9 g, 71%).
Synthesis of compound (L)
The overall synthetic sequence is reported in Fig. 1. Product 1
has already been reported in ref. 19. To prepare compound 2,
10 g of 1 (0.018 mol) were dissolved in 150 cm3 of CHCl3 and
placed in a round-bottom flask, to which 50 g of triethylamine
were slowly added. 300 cm3 of CHCl3 containing 21 g of p-
toluenesulfonyl chloride were added dropwise, under stirring,
to the resulting solution. The reaction mixture was left at room
temperature, under stirring, for at least 24 h, after which the
solvent was evaporated under vacuum. The sticky oil obtained
was dissolved in hot isopropanol and the resulting solution was
left to cool overnight. The two phases were then separated: the
solid phase was discharged while the liquid alcoholic phase
was concentrated under vacuum, obtaining a white solid. The
product was recrystallised from ethanol, yielding 11 g (69%).
Elemental analysis: Anal. Calc. for C45H58N6O9S4: C 56.58; H
6.12; N 8.80. Found: C 56.7; H 6.0; N 8.7%. 1H NMR (CDCl3;
200 MHz): d 7.72 (d, 8H), 7.59 (d, 2H), 7.26 (d, 8H), 7.08 (t, 1H),
5.63 (br, 1H), 3.61 (s, 3H), 3.58 (s, 4H), 2.92 (t, 8H), 2.56 (t, 8H),
2.40 (s, 12H).
Anal. Calc. for C28H58Br6N6O5·H2O: C 31.84, H 5.73, N 7.96;
Found: C 32.0, H 5.6, N 7.7%. MS (ES): m/z 554 (M + H)+
1H NMR (D2O; pH = 3): d 7.28 (d, 2H), 6.97 (t, 1H), 3.93
(s, 4H), 3.71 (t, 8H), 3.64 (s, 8H), 3.26 (t, 8H), 3.17 (t, 8H), 3,02
(t, 8H).
13C NMR (D2O; pH = 3): d 155.0, 133.5, 124.4, 123.1, 70.9,
66.5, 55.3, 50.6, 47.6, 44.7.
Compound L1·6HBr
Preparation of compounds 38-methoxy-4,13,19,28-tetrakis(4-
toluensulfonyl)-1,4,13,16,19,28-hexaaza-7,10,22,25-tetra-
oxatricyclo[14.14.7.132,36]octatriconta-32,34,D36,38-triene 4 and
2,6-bis[4,13-bis(4-toluensulfonyl)1,4,13-triaza-7,10-dioxacyclo-
pentadec-1-ylmethyl]-1-methoxybenzene 5
By treating compound 5 as already described for compound
4, 0.53 g (73%) of the hexahydrobromide salt of L1 were
obtained.
Anal. Calc. for C28H58Br6N6O5·2H2O: C 31.31, H 5.82, N 7.82;
Found: C 31.2, H 5.9, N 7.7%. MS (ES): m/z 554 (M + H)+
1H NMR (D2O; pH = 3): d 7.22 (d, 2H), 6.85 (t, 1H), 3.79
(s, 4H), 3.68 (t, 8H), 3.61 (s, 8H), 3.18 (t, 8H), 3.03 (m, 16H).
13C NMR (D2O; pH = 3): d 154.9, 133.8, 124.1, 123.0, 70.7,
67.3, 54.6, 51.1, 46.9, 44.3.
15.5 g of 2 (0.016 mol) and 80 cm3 of dry ethanol, were mixed
in a three-neck round-bottom flask, equipped with condenser,
drying tube and nitrogen inlet. The solution was heated to
reflux and then freshly made sodium ethanolate (1.7 g of 3
dissolved in 60 cm3 of absolute ethanol) was quickly added.
After a few min a white solid formed and the reaction mixture
was left under stirring for 2 h. The solvent was removed from
the reaction mixture by distillation under nitrogen, after which
the resulting white sodium salt was dried under vacuum. The
solid obtained was suspended in 500 cm3 of dry DMF and
the reaction mixture heated to 110 °C. 14.9 g (0.032 mol) of
tri(ethylene glycol) di-p-tosylate 3 (Aldrich Chemical) dissolved
in 300 cm3 of dry DMF were added dropwise to the previously
stirred solution over a period of 6 h. The reaction mixture was
left under reflux for a further 2 h, after which half of the solvent
was slowly evaporated, and the solution obtained poured into
a beaker containing a mixture of water and ice. The brownish
solid which formed was filtered off, washed with water and dried
[Ni2H−1L(N3)3]·EtOH (6)
A sample of Ni(ClO4)2·6H2O (36.6 mg, 0.1 mmol) in ethanol
(20 mL) was slowly added to an ethanolic solution (30 mL)
of L (27.4 mg, 0.05 mmol). The resulting solution was stirred
at room temperature for 10 min, after which NaN3 (12.8 mg,
0.2 mmol) was added. The slow evaporation of the solvent led to
crystallization of complex 6 as green crystals suitable for X-ray
analysis.
[Cu2H−1L(N3)](ClO4)2 (7)
A sample of Cu(ClO4)2·6H2O (37.1 mg, 0.1 mmol) in ethanol
(20 mL) was slowly added to an ethanolic solution (30 mL)
3 4 7 2
D a l t o n T r a n s . , 2 0 0 4 , 3 4 6 8 – 3 4 7 4

View Article Online
Table 3 Crystal data and refinement parameters for 6 and 7 (refinement method: full-matrix least-squares on F 2)
6
7
Empirical formula
M
C30H57N15Ni2O6
841.33
C28H51N9O13Cu2Cl2
919.76
T/K
k/Å
298
1.54184
298
1.54184
Crystal system
Space group
a/Å
b/Å
c/Å
Monoclinic
C2/c
24.077(1)
12.677(1)
13.632(1)
Orthorhombic
Pbca
19.624(4)
19.449(4)
21.008(5)
b/°
112.576(5)
3842.0(4)
4, 1.455
V/Å3
8018(3)
8, 1.524
3.141
Z, Dc/g cm−3
l/mm−1
1.736
F(000)
1784
3824
0.2 × 0.2 × 0.4
3.83–58.01
−18 to 21, −20 to 20, −21 to 22
31699/5510
1837/0/238
Crystal size/mm
h Range for data collection/°
Limiting indices, hkl
Reflections collected/unique
Data/parameters
Goodness-of-fit on F 2
Final R indices [I > 2r(I)]
0.3 × 0.4 × 0.5
3.98–64.14
−28 to 1, −1 to 14, −14 to 15
3706/3150
2779/0/257
1.081
0.905
R1 = 0.0424, wR2 = 0.1219
R1 = 0.0989, wR2 = 0.2352
Table 4 Selected bond lengths (Å) for compounds 6 and 7
of L (27.4 mg, 0.05 mmol). The resulting solution was stirred
at room temperature for 10 min, after which NaN3 (12.8 mg,
0.2 mmol) was added. The slow evaporation of the solvent led
to crystallization of complex 7 as green crystals suitable for
X-ray analysis.
6
7
Ni(1)–O(1)
Ni(1)–N(1)
Ni(1)–N(2)
Ni(1)–N(7)
Ni(1)–N(3)
Ni(1)–N(4)
2.054(2)
2.084(2)
2.084(2)
2.093(2)
2.164(2)
2.168(3)
Cu(1)–O(1)
Cu(1)–N(1)
Cu(1)–N(2)
Cu(1)–N(7)
Cu(1)–N(3)
1.997(8)
2.03(1)
2.02(1)
2.02(1)
2.24(1)
EMF measurement
Equilibrium constants for L protonation and complexation
reactions were measured by pH-metric methods (pH = −log[H+])
in 0.15 mol dm−3 NaCl at 298.15 ± 0.1 K using the fully auto-
matic equipment that has already been described.20 The EMF
data were collected with the PASAT computer program.21
The combined glass electrode was calibrated as a hydrogen
concentration probe by titrating known amounts of HCl with
CO2-free NaOH solutions and measuring the end point by
Gran’s method,22 which provides both the standard potential
E° and the ionic product of water (pKw = 13.73(1) at 298.1 K in
0.15 mol dm−3 NaCl, Kw = [H+][OH−]). At least three potentio-
metric titrations were performed for each system in the pH
range 2–11, using different molar ratio of M(II)/L ranging from
1:1 to 2:1. All titrations were treated either as single sets or as
separate entities, for each system; no significant variations were
found in the values of the determined equilibrium constants.
The HYPERQUAD computer program was used to process all
potentiometric data.23
Cu(2)–O(1)
Cu(2)–N(4)
Cu(2)–N(5)
Cu(2)–N(7)
Cu(2)–N(6)
1.981(8)
2.04(1)
2.03(1)
2.06(1)
2.23(1)
For compound 6, anisotropic thermal parameters were
used for the non H-atoms while an overall isotropic thermal
parameter was used for the hydrogen ones. The latter atoms
were all introduced in calculated positions with the exception
of the hydrogen atoms of the ethanol molecule, which were
not set. The ethanol molecule is near an inversion center and
a population factor of 0.5 was assigned to the O(4), C(16) and
C(17) atoms.
Because of the poor observed reflections/parameters
ratio, in compound 7 only the Cu and Cl atoms were refined
anisotropically, while all the others were treated isotropically.
The hydrogen atoms were set in calculated positions and refined
with a thermal parameter depending on the atom to which they
are bound.
X-Ray crystallography
For compound [Ni2(H−1L)(N3)3]·EtOH 6 intensity data were
collected on a Siemens P4 four-circle diffractometer using
graphite-monochromated Cu-Ka radiation (k = 1.54184 Å),
T = 298 K. Data were corrected for Lorentz and polarization
effects. Absorption correction was performed with the
DIFABS24 program.
Intensity data for compound [Cu2(H−1L)(N3)](ClO4)2 7 were
collected on a Siemens/Bruker diffractometer equipped with
rotating anode and CCD area detector, using Cu-Ka radiation
(k = 1.54184 Å), T = 298 K and the SMART program.25
Six settings of x were run and narrow data “frames” were
collected for 0.3° increments in x. A total of 3300 frames of
data were stored, providing a sphere of data. Data reductions
were performed with the SAINT 4.0 program.26 Absorption
corrections were performed with the program SADABS.27
Both structures were solved by direct methods using the
SIR97 program28 and refined by full-matrix least squares against
F 2 using all data (SHELX9729).
Geometrical calculations were carried out by PARST9730
and molecular plots were produced by the ORTEP3
program.31 Table 3 reports details of the crystal data, data
collection, structure solution and refinement. Tables 4 and
5 list the bond distances and angles defining the metal
environments.
CCDC reference numbers 235120 and 235121.
See http://www.rsc.org/suppdata/dt/b4/b408808e/ for crystal-
lographic data in CIF or other electronic format.
Acknowledgements
Financial support from the Italian Ministero dell’Università e
della Ricerca Scientifica e Tecnologica (PRIN2002) and CRIST
(Centro Interdipartimentale di Cristallografia Strutturale,
where all the X-ray measurements were carried out) are
gratefully acknowledged.
D a l t o n T r a n s . , 2 0 0 4 , 3 4 6 8 – 3 4 7 4
3 4 7 3

View Article Online
Table 5 Selected angles (°) for compounds 6 and 7
6
7
O(1)–Ni(1)–N(1)
O(1)–Ni(1)–N(2)
O(1)–Ni(1)–N(3)
O(1)–Ni(1)–N(4)
O(1)–Ni(1)–N(7)
N(1)–Ni(1)–N(2)
N(1)–Ni(1)–N(3)
N(1)–Ni(1)–N(4)
N(1)–Ni(1)–N(7)
N(2)–Ni(1)–N(3)
N(2)–Ni(1)–N(4)
N(2)–Ni(1)–N(7)
N(3)–Ni(1)–N(4)
N(3)–Ni(1)–N(7)
N(4)–Ni(1)–N(7)
89.75(9)
169.72(8)
90.09(7)
82.68(7)
81.09(9)
84.5(1)
81.6(1)
96.5(1)
165.58(9)
97.4(1)
89.5(1)
O(1)–Cu(1)–N(1)
O(1)–Cu(1)–N(2)
O(1)–Cu(1)–N(3)
93.2(4)
151.2(4)
99.5(3)
O(1)–Cu(2)–N(4)
O(1)–Cu(2)–N(5)
O(1)–Cu(2)–N(6)
91.5(4)
153.7(4)
97.2(4)
O(1)–Cu(1)–N(7)
N(1)–Cu(1)–N(2)
N(1)–Cu(1)–N(3)
78.8(4)
86.3(4)
82.0(4)
O(1)–Cu(2)–N(7)
N(4)–Cu(2)–N(5)
N(4)–Cu(2)–N(6)
78.2(4)
86.5(4)
83.5(4)
N(1)–Cu(1)–N(7)
N(2)–Cu(1)–N(3)
171.7(4)
108.9(4)
N(4)–Cu(2)–N(7)
N(5)–Cu(2)–N(6)
169.6(4)
108.6(4)
106.2(1)
172.6(1)
87.27(7)
93.34(8)
N(2)–Cu(1)–N(7)
N(3)–Cu(1)–N(7)
101.7(4)
97.0(4)
N(5)–Cu(2)–N(7)
N(6)–Cu(2)–N(7)
103.3(4)
96.2(4)
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D a l t o n T r a n s . , 2 0 0 4 , 3 4 6 8 – 3 4 7 4