Synthesis, characterization, and fluorescence behavior of four novel macrocyclic emissive ligands containing a flexible 8-hydroxyquinoline unit

Article abstract of DOI:10.1016/j.tet.2009.05.046

Four emissive macrocyclic ligands mono-substituted with an 8-hydroxyquinoline pendant arm are presented. The new compounds have been used for metal-ion detection, which results from the competition between PET (photo-induced electron transfer) and PPT (ph

Full text of DOI:10.1016/j.tet.2009.05.046

Tetrahedron 65 (2009) 6179–6188
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis, characterization, and fluorescence behavior of four novel macrocyclic
emissive ligands containing a flexible 8-hydroxyquinoline unit
a
,
,
b
c
a
Cristina Nunez b, Rufina Bastida b , Alejandro Macıas , Emilia Bertolo , Luz Fernandes ,
*
´ ˜
´
´
Jose Luis Capelo d, Carlos Lodeiro a
a,
,e,
*
´
a REQUIMTE, Department of Chemistry, FCT-UNL, 2829-516 Monte de Caparica, Portugal
b Inorganic Chemistry Department, Faculty of Chemistry, University of Santiago de Compostela, E15782, Spain
c Department of Geographical and Life Sciences, Canterbury Christ Church University, Canterbury, Kent, UK
d BIOSCOPE Group, Analytical & Food Chemistry Department, Faculty of Science, University of Vigo, Campus of Ourense, E32004 Ourense, Spain
e BIOSCOPE Group, Physical-Chemistry Department, Faculty of Science, University of Vigo, Campus of Ourense, E32004 Ourense, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Four emissive macrocyclic ligands mono-substituted with an 8-hydroxyquinoline pendant arm are
presented. The new compounds have been used for metal-ion detection, which results from the
competition between PET (photo-induced electron transfer) and PPT (photo-induced proton transfer)
mechanisms. Solid metal complexes with divalent Cu(II), Zn(II), and Cd(II), and trivalent metal ions Al(III)
and Cr(III) have been also synthesized and characterized. The compounds have been isolated as
mononuclear or dinuclear (Cu(II)) complexes, confirming the stoichiometry observed in solution.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 19 March 2009
Received in revised form 8 May 2009
Accepted 18 May 2009
Available online 23 May 2009
Keywords:
Chemosensor
Fluorescence
8H-Quinoline
Aluminum(III)
Chromium(III)
Zinc(II)
1. Introduction
their guest-modulated chromogenic and fluorescent behavior.
Accordingly, they have been used in chromatography,4 for the
The development of compounds that selectively respond to
specific metal ions and thus can be used as ion sensors is an area of
growing interest.1 Emphasis has been placed on the development of
compounds that can detect the presence of specific metal ions
through guest-modulated effects, e.g., changes in redox potentials,2
UV–vis absorption spectra,3 or fluorescence spectra1 as a result of
the interaction between the sensor and the target ion. Particular
attention has been paid to fluorescence chemosensors, since fluo-
rescence modulation allows the detection of the target ions at very
low concentrations;1b moreover, fluorescent sensors offer several
distinct advantages such as selectivity, time response, and spatial
resolution.
detection of metal ions,5 in the preparation of organic light emitting
diode devices,6 in electrochemiluminiscence,7 etc. 8-HQ forms
stable five-membered chelate rings with metal centers, and very
stable complexes of the type M(HQ)þ, M(HQ)2 or M(HQ)3 with
divalent transition and post-transition metal ions.8 Macrocycles
containing quinoline side arms have been employed as analytical
reagents in absorption spectrometry, fluorometry, solvent extrac-
tion, and chromatography.9 The potential use of some of these
compounds as pesticides has also been explored.10
A number of azacrown ethers containing 8-hydroxyquinoline
(I,11 II,5c III12), 5-chloro-8-hydroxyquinoline (IV5c), and 8-hydroxy-
5-N,N-dimethylaminosulfonylquinoline (V12) have been reported
(see Scheme 1). Prodi5a and co-workers reported systems VI.a and
VI.b for the recognition of Mg(II) and Hg(II), respectively. In these
complexes, the pKa values for the hydroxyl groups of the 8-HQ
moieties were low enough to become fluorescent in slightly acidic
solutions.5c,10,13 Addition of Mg(II) to VI.a or Hg(II) to VI.b in neutral
MeOH–H2O (1:1) solutions results in the strong enhancement of the
luminescence bands at 520 nm and 476 nm, respectively. All these
ligands have been designed to detect transition and post-transition
8-Hydroxyquinoline (8-HQ) and derived compounds are known
to be the best chelating agents after EDTA and its derivatives, due to
* Corresponding authors. Tel.: þ34 988 38 70 72; fax: þ34 988 38 70 01 (C.L.);
tel.: þ34 981 528073; fax: þ34 981 597525 (R.B.).
E-mail addresses: mrufina.bastida@usc.es (R. Bastida), clodeiro@uvigo.es
(C. Lodeiro).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.05.046

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C. Nu´n˜ez et al. / Tetrahedron 65 (2009) 6179–6188
A
S
N
N
N
N
N
N
N
S
N
S
OH
OH
OH
OH
N
N
A=O, n=0
A=O, n=1
A=S, n=0
A=S, n=1
H3C
CH3
OH
II
n
I
Cl
Cl
O
O
S
N
N
N
N
N
N
N
N
OH
OH
OH
OH
O
O
S
S
O
IV
III
SO2N(CH3)3
R
R
O
O
N
N
N
N
N
NH
NH
N
OH
O
O
OH
Cl
OH
HN
V
VI.a (R = Cl)
VI.b (R = NO2)
Cl
N
N
N
N
N
N
OH
OH
CH3
VII
Scheme 1. Macrocyclic ligands with quinoline pendant arms reported for Pb2þ(I, II, III, VII), Co2þ(I), Ni2þ(I), Cu2þ(I, II), Zn2þ(I, II, III, V, VII), Cd2þ(I, II, III, VII), Hg2þ(VI), Kþ(IV.b),
Mg2þ(VI.a), and Ba2þ(IV).
metal ions through guest associated modulation of the absorption
and fluorescence spectra of the ligands.14 Less attention has been
paid to macrocycles containing a pyridine head. Delgado and co-
workers have published a small tetraaza donor macrocyclic system
(VII) substituted with two 5-chloro-8-hydroxyquinoline units; its
interaction with Cu(II), Zn(II), Cd(II), and Pb(II) were studied, but no
fluorescence data were reported.15
The biological and biomedical significance of Cu(II), Zn(II), Cd(II),
Al(III) or Cr(III) makes the detection of these metal ions crucial.16 The
design and synthesis of fluorescence chemosensors for Cu(II) have
become a very active research area, due to the adverse effects of this
metal ion when present in large concentration.17–19 Elements from
group 12 (Zn(II), Cd(II), and Hg(II)) are also attracting considerable
attention, due to the biological importance of Zn(II) and the
toxicological effects of Cd(II) and Hg(II).20 Zn(II) acts as a catalytic or
co-catalytic factor in the active sites of more than 300 enzymes and,
due to their chemical similarities, Zn(II) can be easily substituted by
Cd(II). Their d10 electron configurations make Zn(II), Cd(II), and
Hg(II) spectroscopically silent; thus, research is now focused on the
design of fluorescence chemosensors capable of determining their
concentration in solution, especially in living cells.21
(sample destructive) methods are used for the analysis of both
metal ions; however, fewer examples of the use of fluorescence
chemosensors (a non-destructive technique) have been reported.
Most of the research has focused on chemosensors for aluminum,22
but less attention has been paid to the detection of chromium.23
As an extension of our work on the synthesis of macrocyclic re-
ceptors possessing pyridine units24 for metal-ion chelation, herein
we report the synthesis and characterization of four new emissive
macrocycles, L1–L4 (see Scheme 2). The starting material for L1 and L2
was the N5O2-donor ligand L, containing a free amine pendant arm.25
The precursor to L3 and L4 (L0) was obtained via Schiff-base conden-
sation of 2,2-(1,3-phenylenebis(methyleneoxy))dibenzaldehyde, and
tris(2-aminoethyl)amine (tren-amine), followed by an in situ re-
ductive demetalation reaction with NaBH4. Condensation of an 8-
hydroxyquinoline unit with the free amine pendant arm yielded the
macrocycles L1–L4. The new ligands have been fully characterized by
the usual techniques.
The protonation behavior and sensing capability toward di-
valent Cu(II), Zn(II), and Cd(II), and trivalent Al(III) and Cr(III) metal
ions have been studied by UV–vis and fluorescent emission
spectroscopy, and by MALDI-TOF-MS spectrometry. In order to
compare with the results obtained in solution, some solid metal
complexes with the same metal ions were synthesized and char-
acterized; these results are also discussed.
Al(III) is widely used in water treatment, as food additive and in
medicine; Cr(III) is used in harden and stainless steel, in alloys to
prevent corrosion, and as inorganic catalyst. Many analytical

C. Nu´n˜ez et al. / Tetrahedron 65 (2009) 6179–6188
6181
X
O
O
O
O
P
P'
Abs. EtOH
NH2
1. H2N
N
N
NH2
O
O
O
O
2. NaBH4
NH
HN
N
NH
HN
N
H2N
Q =
H
H2N
L'
N
L
OH
O
1. Q
1. Q
Q
Q
2. NaBH4
2. NaBH4
N
O
N
O
O
O
O
O
O
O
NH
NH
NH
NH
HN
N
HN
HN
HN
N
N
N
NH
N
NH
N
N
N
N
N
OH
OH
OH
OH
L2
L1
L4
L3
Scheme 2. Schematic synthetic route for ligands L1–L4 in absolute ethanol.
2. Results and discussion
n(C]N) vibrations of the pyridine groups appear in the expected
positions, 1597, 1453 cmꢀ1, and 1600, 1453 cmꢀ1, respectively. The
MALDI-TOF-MS spectrum of L1 shows a parent peak at m/z 617,
corresponding to the protonated form of the ligand [L1H]þ. For L3,
the base peak in the FAB mass spectrum and in the MALDI-TOF-MS
was at m/z 616, attributable to the protonated form [L3H]þ.
Elemental analysis data confirm that both Schiff-base ligands have
been isolated. L1 and L3 were studied by 1H NMR in CDCl3; the
spectra confirm the integrity of the ligands in solution (Table 1).
Both 1H NMR spectra show a peak at ca. 8.2 ppm, corresponding to
the imine protons, and no signals corresponding to the primary
amine or aldehyde protons are present.
2.1. Synthesis and characterization of the free
ligands L1–L4 and metal complexes
2.1.1. Schiff-base macrocycles L1 and L3
We have previously reported the synthesis of the macrocycle L25
obtained by a template cyclocondensation of tren-amine with 2,6-
bis(2-formylphenoxymethyl)pyridine (P).26 Macrocyclic ligand L0 was
synthesized by the same template method, via cyclocondensation of
tren-amine with 2,2-(1,3-phenylenebis(methyleneoxy))dibenzalde-
hyde (P0) in the presence of Ba(ClO4)2$2H2O, followed by an in situ
demetalation reaction with NaBH4.
Subsequent condensation of L and L0 with 8-hydroxyquinoline-
2-carbaldehyde using a one-step procedure, yielded L1 and L3; both
ligands were isolated as air-stable orange solids, ca. 73.3% and 62.3%
yield, respectively. The infrared spectra (KBr discs) show bands at
1642 (L1) and 1641 (L3) cmꢀ1, corresponding to the imine bond, and
no peaks attributable to unreacted amine or carbonyl groups were
2.1.2. Synthesis and characterization of the amine
macrocycles L2 and L4
Following a one-step procedure involving the reduction of L1 and
L3 with NaBH4, macrocyclic ligands L2 and L4 were isolated as air-
stable yellow solids, ca. 45.3 and 59.4% yield, respectively. The
absence of a band at ca. 1640 cmꢀ1 in the infrared spectra (KBr disc)
confirms the reduction of the imine group. The absorption bands
present. The absorption bands corresponding to the n(C]C) and
Table 1
1H NMR shifts (ppm) for L1, L2, L3, and L4 in CD3Cl solutions (see Scheme 3 for labeling)
L1
L2
L3
L4
H1,2; H4–7; H16–20
H3
7.9–6.7 (m), 16H
4.9 (s), 4H
7.8–6.8 (m), 16H
5.3 (s), 4H
8.1–6.7 (m), 17H
5.1 (s), 4H
8.0–6.5 (m), 17H
5.0 (s), 4H
H8
3.7 (m), 4H
3.4 (m), 6H
2.5 (m), 6H
8.2 (s), 1H
3.7–3.6 (m), 4H
3.6–3.5 (m), 6H
2.8–2.3 (m), 6H
4.0 (s), 2H
3.8 (s), 4H
3.7 (s), 4H
H10,13
H11,12
H15
2.9–2.1 (m), 6H
2.9–2.1 (m), 6H
8.4 (s), 1H
2.6–2.1 (m), 6H
2.6–2.1 (m), 6H
3.4 (s), 2H
H21
5.6 (s), 1H
5.9 (s), 1H
4.5 (s), 1H
4.0 (s), 1H

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C. Nu´n˜ez et al. / Tetrahedron 65 (2009) 6179–6188
1
associated with n(C]C) and n(C]N) vibrations of the pyridine
2
rings, which have undergone a shift toward higher wave numbers
on complexation.27 As in the complexes with L1 and L3, the
presence of an intense broad band at ca. 3400 cmꢀ1 makes it dif-
3
X
4
O
5
6
O
ficult to see the bands corresponding to the n(O–H) and n(N–H),
8
which would appear in this region. The spectra of the nitrate
complexes show a band at 1384 cmꢀ1 associated with the presence
of ionic nitrate. For CdL2(ClO4)2$2C2H6O, bands attributable to the
7
NH
HN9
10
13
N
11
12
16
18
17
asymmetric Cl–O stretching mode at ca. 1088 cmꢀ1
(n3) and the
19
20
asymmetric Cl–O bending mode (n4) at ca. 627 cmꢀ1 can be
observed. The highest energy band shows considerable splitting,
with three maxima at ca. 1050, 1088, and 1121 cmꢀ1, suggesting
some interaction of at least one of the ClOꢀ4 anions with the metal.28
NH14
N
15
OH21
Scheme 3. Ligands L1–L4 with numbered atoms.
corresponding to n(C]C) and n(C]N) vibrations of the pyridine
groups appear at 1597,1451 cmꢀ1, and 1600,1453 cmꢀ1, respectively.
The ESI mass spectrum of L2 shows a peak at 619 amu attributable
to [L2H]þ. For L4, the highest peak in the FAB mass spectrum is at
618 amu, attributable to [L4H]þ. Both peaks were observed also in
the MALDI-TOF-MS spectra. Ligands L2 and L4 were studied by 1H
NMR in CDCl3; the NMR spectra confirm the integrity of the ligands
in solution. The absence of a peak at ca. 8.2 ppm in the 1H NMR
spectra confirms the reduction of the imine protons (see Table 1).
2.2. Spectrophotometric and spectrometric studies
2.2.1. Spectrophotometric studies: UV–vis and Fluorescence
emission spectroscopy
Ligands L1–L4 have a low solubility in water. In addition in
water–absolute ethanol solutions (50:50, v/v) those ligands pre-
cipitated. For the aforementioned reasons all the spectroscopic
studies have been done in absolute ethanol.
The absorption spectra of ligands L1, L2, L3 and L4 in absolute
ethanol solution show one band centered at 248–250 nm, attrib-
2.1.3. Synthesis and characterization of the metal complexes
The coordination ability of ligands L1 to L4 toward hydrated
transition and post-transition metal salts was studied in solution
and in solid state. Reaction of L1 and L3 with Al(III) chloride in a 1:1
metal–ligand ratio in ethanol led to two compounds of formula
[AlL1](Cl)3$5H2O and [AlL3](Cl)3$6H2O in good yields, 55.3 and
59.2%, respectively. The complexes were characterized by elemen-
tal analysis, IR, and ESI MS or FABMS spectra. The reaction was
attempted also with the Zn(II) and Cr(III) salts, but only the alu-
minum products gave satisfactory microanalytical results. The ESI
mass spectrum of [AlL1](Cl)3$5H2O displays peaks corresponding to
the [M2L1]þ, [M2L1Xz]þ (z¼3 and 5) fragments, and the FAB mass
spectrum of [AlL3](Cl)3$6H2O displays a peak corresponding to the
fragment [M3L3X2]þ, confirming the formation of both complexes;
the higher nuclearity suggests some complex formation in the gas
phase. The IR spectra of the complexes were recorded as KBr discs.
In both cases, the band due to the imine bond is shifted to lower
wave numbers when compared to its position in the spectrum of
utable to the
p
–
p transitions in the ligand. The band presents
*
a long tail, up to 400 nm. The spectrum is independent of the acidic
conditions, and addition of up to 5 equiv of HBF4 does not affect the
absorption band; this result is in agreement with other polyamine
macrocyclic ligands containing aromatic units. The spectra for L1
and L2 show an emission band centered at 524 nm. The intensity of
this band increases with the addition of protons, achieving a pla-
teau when 4 equiv of HBF4 is added. The spectra for L3 and L4
(without the pyridine head) show the emission band centered at
514 nm; addition of acid results in an increase of this band, also
achieving a plateau with the addition of 4 equiv. These results
suggest that the pyridine ring present in the macrocyclic skeleton
of L1 and L2 may not be protonated on these conditions. Addition of
a tetrabutylammonium hydroxide solution to an ethanolic solution
of ligands L1 and L3 reduced the intensity of the emission in ca. 50%;
2 equiv of base is enough to achieve a plateau. A generic spectro-
photometric characterization is shown in Figure 1.
the free ligand, and the n(C]C) and n(C]N) stretching modes of the
pyridine rings appear at higher wave numbers than those on the
spectrum of the free ligand. Both effects suggest that the Npy atom
of the quinoline pendant group could be involved in the co-
ordination to the metal ion.27 The broad absorption band in the
region 3450–3380 cmꢀ1 present is probably due to the existence of
lattice and/or coordinated water in the molecule, and make it
0.35
Emission
Excitation
A
1
A
0.3
0.25
0.2
I norm / a.u.
0.8
0.6
0.4
0.2
0
difficult to see the bands due to the
n(O–H) and n(N–H) stretching
vibrations, which would appear in this region.
Ligands L2 and L4 reacted easily with transition and post-tran-
sition ions producing air-stable solid complexes, which were
characterized by elemental analysis, IR, ESI MS (L2 complexes), and
FABMS (L4 complexes). The elemental analysis data indicate the
formation of mononuclear complexes with empirical formulas
0.15
0.1
CdL2(ClO4)2$xC2H6O,
ZnL2(NO3)2$xH2O,
CrL2(NO3)3$xH2O,
ML4(NO3)2$xH2O (M¼Zn, Cd), CrL4(NO3)3$xH2O, AlL2(Cl)3$xH2O,
AlL4(Cl)3$xH2O and the dinuclear complexes Cu2L2(NO3)4$xC2H6O
and Cu2L4(NO3)4$xH2O. The ESI mass spectra for L2 complexes
display peaks corresponding to the [ML2]þ, [ML2X]þ, [ML2X2]þ,
[M2L2X]þ, [M2L2X2]þ fragments, and the FAB mass spectra for L4
complexes display a peak attributable to the [ML4]þ fragment,
confirming the formation of the complexes in both cases. The IR
spectra of all the complexes were recorded as KBr discs and all
show similar features. As in the free ligands there are split bands
0.05
0
240
320
400
480
560
640
720
800
Wavelength / nm
Figure 1. Absorption, emission, and excitation spectra of ligand L2 in absolute ethanol
solution ([L2]¼1.0ꢁ10ꢀ5 M, lexc¼400 nm, lem¼530 nm).

C. Nu´n˜ez et al. / Tetrahedron 65 (2009) 6179–6188
6183
The relative fluorescence quantum yields of ligands L1 to L4 were
determined using a 0.1 M solution of quinine sulfate in 0.5 M H2SO4
Table 2
Optical data for the metal complexes of L1, L2, L3 and L4 in absolute ethanol solutions
(
lexc¼400 nm; 25 ꢂC)
as standard (
f
¼0.546); the values obtained were always below
ꢀ3 30,29c The fluorescence of chemosensors with 8-HQ units is
Metal complex
lmax (nm); log
3
lem (nm)
1ꢁ10
.
AlL1(Cl)3$5H2O
AlL2(Cl)3$2H2O
AlL3(Cl)3$6H2O
AlL4(Cl)3$5H2O
269; 4.46
261; 4.20
260; 4.19
262; 4.77
546
543
545
545
weak due to the competition between the intermolecular photo-
induced proton transfer (PPT) from the hydroxyl group of the
molecule, and the photo-induced electron transfer (PET) from the
amines.5a Moreover, in proton–donor solvents, a PPT process
involving solvent molecules opens another way to further
deactivate fluorescence. Consequently, both PPT and PET processes
can quench the fluorescence emission in substituted quinolines.
The quenching effect observed after the addition of tetrabutyl-
ammonium hydroxide is consistent with this explanation; in this
case, the PET mechanism is stronger than the PPT.
CrL2(NO3)3$6H2O
CrL4(NO3)3$2H2O
255; 4.61
251; 4.61
535
536
Cu2L2(NO3)4$3C2H6O
Cu2L4(NO3)4$3H2O
266; 4.80
275; 4.35
d
d
ZnL2(NO3)2$6H2O
ZnL4(NO3)2$3H2O
265; 4.41
273; 4.21
573
565
CdL2(ClO4)2$2C2H6O
CdL4(NO3)2$3H2O
260; 4.56
248; 4.17
269; 4.18
300; 3.76
508
505
The sensing behavior of the compound toward Zn(II), Cd(II),
Cu(II), Al(III), and Cr(III) has been studied in solution, using absolute
ethanol as the solvent. For comparison purposes, all the synthe-
sized metal complexes have been also optically characterized and
the data are given in Table 2.
Addition of increasing amounts of anhydrous zinc and cadmium
triflates to an ethanolic solution of L2 or L4 (1.00Eꢀ5 M), at 298 K, led
to a decrease in the absorption band centered at 249 nm, and the
appearance of a new band centered at ca. 270 nm. This spectrum
has a long tail up to 400 nm. In this region, the absorption increases
with the addition of metal ions, suggesting the involvement of the
quinoline ring in the metal complexation. An isosbestic point at
260 nm was observed for all the metal titrations, confirming the
presence of two species in solution, the free ligand, and the metal
The photophysical properties of compounds including 8-HQ as
chromophore have been studied in detail.29 In their fluorescence
spectra, a non-structured band centered between 360 and 460 nm,
strongly dependent on the solvent, was observed.29 In our case, the
emission band is red-shifted in at least 60 nm, which could facili-
tate their potential applications in biological systems. The emissive
compounds could be irradiated in the presence of bio-molecules
without any damage to the chromophores present in aminoacids,
peptides, proteins, DNA, etc.
0.3
A
1.0
0.3
1
1
I555 nm / a.u.
0.8
A
0.25
0.24
0.6
0.8
0.18
0.4
0.2
0.5
0.2
0.12
0.6
0
0.15
0
0.5
1
1.5
2
0.06
0
248 nm
270 nm
[Zn2+] / [L2]
0.4
0.2
0
0.1
0.05
0
0
0.5
1
1.5
2
[Zn2+] / [L2]
0
A
B
480
560
640
720
Wavelength / nm
800
880
250
300
Wavelength / nm
350
400
450
0.3
1.0
0A.3
A
1
0.8
0.6
0.4
0.2
0
1
0.8
0.6
0.4
0.2
0
0.25
0.25
0.2
0.15
0.1
0.5
0.2
0.15
0.1
248 nm
270 nm
0.05
0
0
0.5
1
1.5
2
[Cd2+] / [L2]
0
0.5
1
1.5
2
[Cd2+] / [L2]
0
0.05
0
C
D
480
560 640
Wavelength / nm
720
800
880
250
300
Wavelength / nm
350
400
450
Figure 2. Absorption (A and C) and fluorescence emission (B and D) titration of absolute ethanol solutions of L2 as a function of increasing amounts of Zn2þ (A and B) or Cd2þ (C and
D) ions. The inset shows the absorption at 248 and 270 nm, and the normalized fluorescence intensity at 555 nm ([L2]¼1.00ꢁEꢀ5 M, lexc¼400 nm).

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C. Nu´n˜ez et al. / Tetrahedron 65 (2009) 6179–6188
0.3
A
0.3
A
1
0.8
0.6
0.4
0.2
0
0
1
0.25
0.2
0.15
0.1
0.05
0
249 nm
267 nm
0.25
0.2
0.8
0.6
0.4
0.2
0
0
0.5
1
1.5
2
2.5
3
1
[Cu2+] / [L3]
0.15
0
0.5
1
1.5
2
2.5
3
[Cu2+] / [L3]
A
B
2
480
560
640
Wavelength / nm
720
800
880
250
300
Wavelength / nm
350
400
450
Figure 3. Absorption (A) and fluorescence emission (B) titrations of absolute ethanol solution of L2 as a function of increasing amounts of Cu2þ ions. The inset shows the absorption
at 249 and 257 nm, and the normalized fluorescence intensity at 555 nm ([L2]¼1.00ꢁEꢀ5 M, lexc¼400 nm).
complex. As an example, Figure 2 depicts the absorption and
emission metal titration of L2 with Zn(II) and Cd(II).
Excitation at 400 nm (quinoline tail) gave emission spectra
centered at 555 nm. The band is red-shifted upon complexation, as
it can be seen in Figure 2B and D for Zn(II) and Cd(II), respectively.
The same behavior was observed when the metal ion used was
As it can be seen in Figure 2A and B, a plateau is reached after
addition of one metal equivalent, suggesting that the macrocyclic
unit is coordinated to one metal ion. This result confirms the stoi-
chiometry observed for the solid metal complexes synthesized.
Copper(II) ions are well know to quench excited states.31 Addition
of increasing amounts of all dn metals studied leads to the forma-
tion of non-emissive complexes. These results are in agreement
with the fluorescence behavior observed for the analytically pure
complexes isolated (see Experimental section).
Al(III).
A Chelation Enhanced Fluorescence (CHEF) effect was
observed in all cases. This well known phenomenon is consistent
with the involvement of the amines and the quinoline ring in
complexation. The lone pairs of the nitrogen atom are bound to the
metal ion preventing the PET processes, while the 8-HQ is
coordinated to the metal preventing the PPT process; thus, com-
plexation results in an enhancement of the fluorescence signal.
Figure 3 shows the absorption and emission spectra of L2 in the
presence of increasing amounts of Cu(II); the inset shows the
normalized fluorescence intensity at 555 nm. Upon addition of
2 equiv of metal ion, the emission disappears, achieving a plateau;
Figure 4. (A) MALDI-TOF-MS spectra of L2 using dithranol as MALDI matrix, (B) in the presence of 1 equiv of Zn(II), and (C) in the presence of 2 equiv of Zn(II).

C. Nu´n˜ez et al. / Tetrahedron 65 (2009) 6179–6188
6185
this suggests the formation of a dinuclear complex. A similar CHEQ
effect was observed in the presence of Cr(III), but the plateau was
achieved for one metal ion, suggesting the formation of a mono-
nuclear complex. Both results agree with the stoichiometry found
in the solid metal complexes synthesized.
Protonation and/or complexation of a pyridine ring lead to
a quenching effect for molecules that incorporate both a pyridine
and an emissive chromophore unit in their structure.32 The pres-
ence of the pyridine head in L1 and L2 creates another inverse PET
mechanism for quenching the emission. The analogous ligands L3
and L4, without the pyridine unit, were synthesized for comparative
purposes. Unfortunately, the results observed with L3 and L4 are
similar to those ligands L1 and L2, due to the strong PPT and PET
processes mentioned previously.
N
O
O
N
O
O
Na+
NH
HN
N
H
NH
HN
N
NH2
[L2Na]+ = 441.2 m/z
[L2-MeQuin]+ =462.2 m/z
The fluorescence quantum yields for all the complexes have
been calculated using a solution of quinine sulfate as pattern. In all
cases, and in accordance with the results obtained for the free
ligands, the values are very small, always below 10ꢀ3. This
quenching can be attributed to the high number of donor atoms
present in the ligands; some of them may not be coordinated to the
metal centers, specially the nitrogens that activate the quenching
through the PET phenomena. As it can be observed in Table 2, the
maximum of the emission for each metal complex is slightly dif-
ferent, opening up the possibility of using these ligands to recog-
nize these metals in solution.
N
N
O
O
O
O
NH
HN
N
NH
N
HN
-O
NH
N
N
N
N
OH
2.2.2. Spectrometric studies by MALDI-TOF-MS spectrometry
OH
Taking into account the biological importance of Zn(II) ions, and
the environmental problems by Al(III) excess, these two metal ions
were selected for the gas phase studies by MALDI-TOF-MS using
ligands L2 and L4 as molecular probes. To perform the metal titra-
tions, both ligands were dissolved in chloroform and the metal salts
in absolute ethanol. Two different strategies were explored. First,
[L2H]+ = 619.3 m/z
[L2-MeQuin]+ = 774.3 m/z
three solutions containing the ligand (1
mL), the MALDI matrix
(dithranol), and the metal salt (1 L) were mixed and then applied
m
in the MALDI-TOF sample holder. The second method consisted of
a layer by layer addition: a solution of L2 or L4 mixed with the
matrix (dithranol) was spotted in the MALDI-TOF plate and then
N
N
O
O
N
O
O
N
dried; subsequently, 1 mL of the solution containing the metal salt
Zn2+
Zn2+
was placed on the sample holder, which was then inserted in the
ion source. For the second case, the chemical reaction between the
ligand and the metal salts occurred in the holder, and the complex
species were produced in gas phase.
HN
HN
N
N
NH
NH2
[L2Zn-MeQuin]+ = 524.1 m/z
The results were the same in both cases. Addition of one metal
equivalent led to the formation of the mononuclear complex.
Addition of increasing amounts of metal ion did not produce any
peaks attributable to the formation of dinuclear complexes. The re-
sults with Al(III) and Zn(II) confirm both the stoichiometry observed
in the synthesized solid metal complexes, and the data obtained in
solution by absorption and fluorescence emission spectroscopy.
Figure 4 summarizes the MALDI-TOF-MS spectra for ligand L2. In
the presence of 1 and 2 equiv of Zn(II), peaks at m/z 619.3, attribut-
able to the protonated ligand [L2H]þ, and m/z 462.2, attributed to the
loss of the methyl-8-HQ group, were observed. Small peaks at higher
mass values, attributable to species with two, three and four pendant
arms, can be observed; these are indicative of the interaction of the
quinoline group with the ligand in the gas phase (see Scheme 4).
After addition of the metal salt, the peak corresponding to the pro-
tonated ligand disappears, and new peaks at m/z 682.3, 524.2, and
441.2, attributable to the [L2Zn–H]þ, [L2Zn–MeQuinoline]þ, and
[L2Na-pendant]þ species, respectively, were observed.
N
OH
[L2Zn-H]+ = 682.3 m/z
Scheme 4. MALDI-TOF-MS fragmentation peak observed for L2 and L2Zn(II) complex.
and sensing capability of these ligands toward divalent, Cu(II),
Zn(II), Cd(II), and trivalent, Al(III) and Cr(III) metal ions have been
studied by UV–vis and fluorescent emission spectroscopy. Several
metal complexes have also been synthesized and characterized,
confirming the stoichiometry and all the data obtained in solution.
The photophysical characterization of the ligands shows two
quenching mechanisms active, PPT and PET. Coordination with
Zn(II), Cd(II), and Al(III) partially prevents this quenching trough
a CHEF effect. Cu(II) and Cr(III) gave non-emissive complexes due to
the quenching, via a CHEQ effect, of the low emission observed for
the free macrocycles. Both phenomena could be used for sensing
purposes, opening up the possibility of using these ligands in
solution for metal-ion recognition.
3. Conclusions
Titrations of L2 and L4 with Zn(II) and Al(III) solutions were
followed by MALDI-TOF-MS spectrometry. In all cases, the forma-
tion of the complex peak was observed. These results confirm the
formation of the metal complexes also in the gas phase.
Four macrocyclic ligands containing an 8-HQ pendant arm have
been synthesized and fully characterized. The protonation behavior

6186
C. Nu´n˜ez et al. / Tetrahedron 65 (2009) 6179–6188
4. Experimental
4.3. Synthesis
4.1. General
4.3.1. Synthesis of 2,2-(1,3-phenylenebis(methyleneoxy))-
dibenzaldehyde
The chemical analysis of the dialdehyde precursor, 2,2-(1,3-
phenylenebis(methyleneoxy))dibenzaldehyde, was carried out on
a Carlo Erba 1106 CHN analyser. Elemental analyses of the ligands
were performed on a Fisons Instruments EA1108 micro analyser by
the Universidade de Santiago de Compostela. The IR spectra of the
precursors were recorded on a Pye Umicam SP3-100 infrared
spectrometer. Infrared spectra of free ligands were recorded as KBr
discs on a BIO-RAD FTS 175-C spectrometer. FAB mass spectra were
recorded using a KRATOS MS50TC spectrometer with 3-nitrobenzyl
alcohol as the matrix. The 1H NMR spectrum of the dialdehyde
precursor was recorded on a JEOL GSX 270 FT NMR spectrometer.
The 1H, 13C NMR, COSY, DEPT, and HMQC spectra were recorded on
a Bruker 500 MHz spectrometer, using CD3Cl as the solvent.
MALDI-TOF-MS spectra have been performed in a MALDI-TOF-
MS model Voyager DE-PRO Biospectrometry Workstation equipped
with a nitrogen laser radiating at 337 nm from Applied Biosystems
(Foster City, United States) from the MALDI-TOF-MS Service of the
REQUIMTE, Chemistry Department, Universidade Nova de Lisboa.
The acceleration voltage was 2.0ꢁ104 kV with a delayed extraction
(DE) time of 200 ns. The spectra represent accumulations of 5ꢁ100
laser shots. The reflection mode was used. The ion source and flight
tube pressures were less than 1.80ꢁ10ꢀ7 and 5.60ꢁ10ꢀ8 Torr, re-
spectively. The MALDI mass spectra of the soluble samples (1 or
A solution of NaOH (1.512 g, 37.8 mmol) in 50 mL of distilled
water was added dropwise to a solution of salicylaldehyde (4.710 g,
37.8 mmol) in 10 mL in absolute ethanol. After heating gently for
approximately 10 min, 1,3-bis(bromomethyl)benzene (4.741 g,
18.9 mmol) was added dropwise. Absolute ethanol (80 mL) was
slowly added, and the resulting solution refluxed gently for 4 h
while maintaining magnetic stirring. The solution was then allowed
to cool and a white solid appeared. The solid was filtered off and
dried. The compound is air stable, soluble in chloroform and
dichloromethane, moderately soluble in hexane, absolute ethanol,
diethyl ether, and methanol and insoluble in distilled water.
C22H18O4$0.5H2O. Mp (ꢂC): 80–85 ꢂC. Anal. Calcd for C22H19O4.5
:
C, 74.36; H, 5.07. Found: C, 74.30; H, 5.04%. Yield: 78%. IR (NaCl
windowsþ, cmꢀ1): 1690 [
n(C]O)], 1600 [n
(C]C)]. MS (FABþ, m/z):
347 [L0H] .
1H NMR (CDCl3),
d (ppm): 10.5 (s), 2H (COH); 7.9–7.0 (m), 12H
(aromatics); 5.2 (s), 4H (aromatic-CH2–O).
4.3.2. Template synthesis of the macrocyclic ligand L0
A solution of tris(2-aminoethyl)amine (0.512 g, 1 mmol) in
methanol (25 mL) was added dropwise to a refluxing solution of
2,2-(1,3-phenylenebis(methyleneoxy))dibenzaldehyde
(0.346 g,
1 mmol) and barium perchlorate (0.336 g, 1 mmol) in methanol
(75 mL). The resulting solution was gently refluxed with magnetic
stirring for ca. 4 h. The solution was allowed to cool and NaBH4
(0.378 g, 10 mmol) was added; magnetic stirring was maintained
for a further 2 h period. The mixture was filtered off and evaporated
to dryness. The residue was then extracted with water–chloroform.
The organic layer was dried over anhydrous Na2SO4 and evaporated
to yield a yellow oil that was dried under vacuum.
2
m mL) such as the ligand and metal complexes were recorded
g/
using the conventional sample preparation method for MALDI-MS.
In the metal titrations by MALDI 1 L of the metal sample was put
m
on the sample holder on which the chelating ligand had been
previously spotted with the matrix (dithranol). The sample holder
was inserted in the ion source. Chemical reaction between the
ligand and metal salts occurred in the holder and complex species
were produced.
C28N4O2H36$4H2O (L0). Anal. Calcd for C28N4O6H44: C, 63.15; H,
8.30; N, 10.53. Found: C, 62.90; H, 8.63; N, 10.85%. Yiþeld: 70.3%. IR
Absorption spectra were recorded on a Shimadzu UV-2501PC or
in a Perkin Elmer lambda 35 spectrophotometer. Fluorescence
emission spectra were recorded on a Horiba–Jobin–Yvon SPEX
Fluorolog 3.22 or a Perkin Elmer LS45 espectrofluorimeters. The
linearity of the fluorescence emission versus concentration was
checked in the concentration range used (10ꢀ4 to 10ꢀ6 M). A cor-
rection for the absorbed light was performed when necessary. All
spectrofluorimetric titrations were performed as follows: the stock
solutions of the ligand (ca. 1ꢁ10ꢀ3 M) were prepared by dissolving
an appropriate amount of the ligand in a 50 mL volumetric flask
and diluting to the mark with absolute ethanol UVA-sol. All mea-
surements were performed at 298 K. The titration solutions (ca.
[L]¼1.0ꢁ10ꢀ5 M) were prepared by appropriate dilution of the
stock solutions. Titrations of the ligand were carried out by addition
of microliter amounts of standard solutions of the ions in absolute
ethanol. HBF4 and tetrabutylammonium hydroxide were used to
change the acidic conditions of the ethanolic solutions. Lumines-
cence quantum yields were measured using a solution of quinine
sulfate in H2SO4 (0.1 M) as a standard [FF]¼0.546].30
(KBr, cmꢀ1): 1601 [ (C]C)]. MS (FAB, m/z): 461 [L0H] .
n
1H NMR of L0 (CDCl3),
d (ppm): 7.7–6.7 (m), 12H (Ph); 5.0 (s), 4H
(Ph–CH2–O); 3.6 (s), 4H (Ph–CH2–NH); 2.6–2.0 (m), 12H (–CH2CH2);
1.7 (s) (–NH).
13C NMR (CDCl3),
d (ppm): 156.9–111.9, 18C (aromatics); 70.2, 2C
(aromatic-CH2-O); 49.1, 2C (aromatic-CH2–NH); 57.5–53.8, 6C
(–CH2CH2).
4.3.3. Synthesis of the imine macrocyclic ligands L1 and L3:
general method
A
solution of 8-hydroxyquinoline-2-carbaldehyde (0.069 g,
0.4 mmol) for L1 (0.034 g, 0.2 mmol) and for L3 in absolute ethanol
(10 mL) was added dropwise to a refluxing solution of L (0.184 g,
0.4 mmol) and L0 (0.092 g, 0.2 mmol) in the same solvent (70 mL for
L1 and 35 mL for L3). The resulting solution was gently refluxed with
magnetic stirring for ca. 4 h. The color changed from yellow to
orange in both cases. The solution was allowed to cool, filtered off to
eliminate the solid precipitate, and then concentrated in the rotary
evaporator. The resulting orange oil was stirred with acetonitrile (to
eliminate possible excess of L or L0) and then with cold diethyl
ether. The orange powder precipitates, later characterized as L1 or
L3, were separated by centrifugation and dried under vacuum.
C37N6O3H40$2H2O (L1). Mp (ꢂC): 170–175. Anal. Calcd for
C37N6O5H44: C, 68.10; H, 6.74; N, 12.88. Found: C, 68.59; H, 6.10; N,
4.2. Chemicals and starting material
Salicylaldehyde, 1,3-bis(bromomethyl)benzene, tris(2-amino-
ethyl)amine, 8-hydroxyquinoline-2-carbaldehyde, and hydrated
chloride, nitrate, and perchlorate salts were commercial products
from Alfa and Aldrich. Solvents used were of reagent grade and
purified by the usual methods. CD3Cl (99.8%) was obtained from
Aldrich. All triflate metallic salts were purchased from Strem,
chemicals for research. The starting materials, 2,6-bis(2-for-
mylphenoxymethyl)pyridine26 and the macrocyclic ligand L25 were
synthesized as previously published.
12.98%. Yield: 73.3%. IR (KBr, cmꢀ1): 1642 [
n
(C]N)imine]; 1597, 1453
[n(C]C) and n
(C]N)py]. MS (ESI, m/z): 617 [L1H]þ; MS (MALDI-TOF-
MS, m/z): 616 [L1H]þ.
1H NMR of L1 (CDCl3),
d
(ppm): 8.2 (s), 1H,(HC]N)imine; 7.9–6.7
(m), 16H (aromatics); 5.6 (s), 1H (OH); 4.9(s), 4H (Py–CH2–O); 3.7
(m), 4H (Ph–CH2–NH); 2.0 (s) (–NH); 3.4–2.5 (m), 12H (–CH2CH2).

C. Nu´n˜ez et al. / Tetrahedron 65 (2009) 6179–6188
6187
C38N5O3H41$3H2O (L3). Mp (ꢂC): 165–170; Anal. Calcd for
was gently heated and magnetically stirred for 4 h. The solution
was then concentrated in a rotary evaporator to ca. 5 mL. A small
volume of diethyl ether (ca. 3 mL) was slowly infused into the so-
lution producing powdery precipitates. The products were sepa-
rated by centrifugation and dried under vacuum. The compounds
were air stable, soluble in ethanol, methanol, and dimethyl sulf-
oxide and insoluble in acetonitrile, ether, and water. Attempts to
grow single crystals of the complexes were unsuccessful.
C38N5O6H47: C, 68.15; H, 7.02; N, 10.45. Found: C, 68.20; H, 7.53; N,
10.08%. Yield: 62.3%. IR (KBr, cmꢀ1): 1641 [
[n(C]C) and n
n
(C]N)imine]; 1600, 1453
(C]N)py]. MS (FABþ, m/z): 616 [L3H]þ. MS (MALDI-
TOF-MS, m/z): 616 [L3H]þ.
1H NMR of L3 (CDCl3),
d
(ppm): 8.4 (s), 1H (C]N)imine; 8.1–6.7
(m), 17H (aromatics); 4.5 (s), 1H (OH); 5.1 (s) 4H (Py–CH2–O); 3.8
(s), 4H (Ph–CH2–NH); 2.9–2.1 (m), 12H (–CH2CH2).
AlL2(Cl)3$2H2O (3). Color: yellow. Anal. Calcd for C37N6O5H46
-
4.3.4. Synthesis of the amine macrocyclic ligands L2 and L4:
general method
Cl3Al: C, 56.25; H, 5.84; N, 10.66. Found: C, 56.83; H, 4.96; N, 11.32%.
Yield: 62.3%. IR (KBr, cmꢀ1): 1604, 1457 [
n(C]C) and n(C]N)py]. MS
NaBH4 was added in excess (20%) to a solution of L1 (0.123 g,
0.2 mmol) and L3 (0.062 g, 0.1 mmol) in methanol at room temper-
ature. The resulting solutions were gently refluxed with magnetic
stirring for 4 h; within that time, the color changed slowly from or-
ange to pale yellow. The mixtures were filtered off and evaporated to
dryness. The residues were then extracted with water–chloroform.
The organic layer was dried over anhydrous Na2SO4 and evaporated
to yield a yellow oil that was stirred with diethyl ether. The yellow
powder formed was separated by centrifugation and dried under
vacuum. These compounds were characterized as L2 and L4.
C37N6O3H42$2H2O (L2). Mp (ꢂC): 175–180; Anal. Calcd for
C37N6O5H46: C, 66.07; H, 7.14; N, 12.50. Found: C, 66.70; H, 6.90; N,
(ESI, m/z): 713 [AlL2Cl2]þ.
AlL4(Cl)3$5H2O (4). Color: yellow. Anal. Calcd for
C38N5O8H53AlCl3: C, 54.26; H, 6.30; N, 8.33. Found: C, 54.35; H, 5.74;
N, 8.15%. Yield: 52.8%. IR (KBr, cmꢀ1): 1603, 1456 [
n
(C]C) and
n
(C]N)py]. MS (FAB, m/z): 618 [L4]þ, 683 [AlL4Cl]þ.
CrL2(NO3)3$6H2O (5). Color: yellow. Anal. Calcd for
C37N9O18H54Cr: C, 46.05; H, 5.60; N, 13.07. Found: C, 46.28; H, 5.79;
N, 13.45%. Yield: 54.4%. IR (KBr, cmꢀ1): 1601, 1457 [
(C]N)py and
n
n
(C]C)]; 839, 1384 [n
(NOꢀ3 )]. MS (ESI, m/z): 619 [L2]þ, 696
[CrL2Na]þ, 754 [CrL2Na(NO3)]þ, 790 [CrL2 (NO3)2]þ.
CrL4(NO3)3$2H2O (6). Color: yellow. Anal. Calcd for
C38N8O14H47Cr: C, 51.17; H, 5.27; N, 12.57. Found: C, 51.23; H, 5.12;
12.20%. Yield: 45.3%. IR (KBr, cmꢀ1): 1597, 1451 [
(C]N)py]. MS (ESI, m/z): 619 [L2H]þ. MS (MALDI-TOF-MS, m/z):
619 [L2H]þ.
1H NMR of L2(CDCl3),
n
(C]C) and
N, 12.87%. Yield: 49.8%. IR (KBr, cmꢀ1): 1601, 1459 [
n(C]C) and
n
n(C]N)py]; 840, 1383 [n
(NOꢀ3 )].
Cu2L2(NO3)4$3C2H6O (7). Color: green. Anal. Calcd for
d
(ppm): 7.8–6.8 (m), 16H (aromatics); 5.9
C43N10O18H60Cu2: C, 45.62; H, 5.30; N, 12.37. Found: C, 45.56; H,
5.28; N,11.90%. Yield: 63.8%. IR (KBr, cmꢀ1): 1599,1454 [
(C]C) and
(s), 1H (OH); 5.3 (s) 4H (Py–CH2–O); 3.7–3.6 (m), 4H (Ph–CH2–NH);
3.6–2.3 (m), 12H (–CH2CH2); 4.0 (s), 2H (8-HQ-CH2NH).
n
n
(C]N)py]; 839, 1384 [n
(NOꢀ3 )]. MS (ESI, m/z): 619 [L2]þ, 680
C38N5O3H43$8H2O (L4). Anal. Calcd for C38N5O11H59: C, 59.90; H.
7.75; N, 9.20. Found: C, 60.57; H, 7.45; N, 8.85%. Yield: 59.4%. IR (KBr,
[CuL2]þ, 766 [Cu2L2(H2O)]þ, 806 [Cu L2(NO3)2]þ, 822
[CuL2(NO3)2(H2O)]þ, 867 [Cu2L2(NO3)2]þ.
cmꢀ1): 1600, 1453 [
n
(C]C) and
n
(C]N)py]. MS (FABþ, m/z): 618
Cu2L4(NO3)4$3H2O (8). Color: green. Anal. Calcd for
C38N9O18H49Cu2: C, 43.60; H, 4.68; N, 12.04. Found: C, 43.25; H,
[L4þH]þ. MS (MALDI-TOF-MS, m/z): 618 [L4H]þ.
1H NMR of L4(CDCl3),
d
(ppm): 8.0–6.5 (m), 17H (Ph); 4.0 (s)
4.20; N,12.04%. Yield: 41.5%. IR (KBr, cmꢀ1): 1602,1458 [
n
(C]C) and
(NOꢀ3 )]. MS (FAB, m/z): 679 [CuL4]þ.
ZnL2(NO3)2$6H2O (9). Color: yellow. Anal. Calcd for
C37N8O15H54Zn: C, 48.50; H, 5.89; N, 12.23. Found: C, 48.50; H, 4.86;
N, 12.44%. Yield: 59.0%. IR (KBr, cmꢀ1): 1600, 1454 [
(C]C) and
(C]N)py]; 839, 1384 [
(NOꢀ3 )]. (ESI,m/z): 619 [L2]þ, 681 [ZnL2]þ.
ZnL4(NO3)2$3H2O (10). Color: yellow. Anal. Calcd for
C38N7O12H49Zn: C, 53.00; H, 5.69; N, 11.39. Found: C, 53.51; H, 5.32;
N, 11.15%. Yield: 68.3%. IR (KBr, cmꢀ1): 1606, 1458 [
(C]C) and
(C]N)py]; 838, 1383 [
(NOꢀ3 )]. MS (FAB, m/z): 639 [L4Na]þ, 680
1H,(OH); 5.0 (s) 4H (Py–CH2–O); 3.7 (s), 4H (Ph–CH2–NH); 2.6–2.1
(m), 12H (–CH2CH2); 3.4 (s), 2H (8-HQ-CH2NH).
n(C]N)py]; 840, 1383 [n
4.3.5. General procedure for metal complexes with ligands L1 and L3
Hydrate aluminum chloride (0.02 mmol) in ethanol (5 mL) was
added dropwise to a stirred solution of L1 or L3 (0.02 mmol) in the
same solvent (15 mL). The resulting mixture was gently heated and
magnetically stirred for 4 h. The solution was then concentrated in
a rotary evaporator to ca. 5 mL. A small volume of diethyl ether (ca.
3 mL) was slowly infused into the solution producing powdery
precipitates. The products were separated by centrifugation and
dried under vacuum. The compounds are air stable, soluble in
absolute ethanol, methanol, and dimethyl sulfoxide and insoluble
in acetonitrile, ether, and water. Attempts to grow single crystals of
the complexes were unsuccessful. This reaction was attempted also
with the Zn(II) and Cr(III) nitrates, but in both cases the microan-
alytical results were unsatisfactory.
n
n
n
n
n
n
[ZnL4]þ, 701 [ZnL4H2O]þ.
CdL2(ClO4)2$2C2H6O (11). Color: brown. Anal. Calcd for
C41N6O13H54Cl2Cd: C, 48.16; H, 5.28; N, 8.22. Found: C, 48.11; H,
5.34; N, 8.51%. Yield: 71.4%. IR (KBr, cmꢀ1): 1599, 1454 [
n
(C]C) and
n
(C]N)py]; 624, 636, 1087, 1109, 1121 [n
(ClOꢀ4 )]. MS (ESI, m/z): 619
[L2]þ, 731 [Cd L2]þ, 929 [CdL2 (ClO4)]þ, 942 [Cd2L2(ClO4)]þ.
CdL4(NO3)2$3H2O (12). Color: brown. Anal. Calcd for
C38N7O12H49Cd: C, 50.25; H, 5.40; N, 10.80. Found: C, 50.70; H, 5.87;
AlL1Cl3$5H2O (1). Color: yellow; Anal. Calcd for C37N6O3H40
Cl3Al$5H2O: C, 52.88; H, 5.95; N, 10.00. Found: C, 52.33; H, 6.31; N,
9.45%. Yield: 55.3%. IR (KBr, cmꢀ1): 1599, 1456 [
(C]C) and
(C]N)py]. MS (ESI, m/z): 619 [L1]þ, 670 [Al2L1]þ, 775 [Al2L1Cl3]þ,
-
N, 10.07%. Yield: 58.3%. IR (KBr, cmꢀ1): 1600, 1454 [
n(C]C) and
n
(C]N)py]; 838, 1384 [
n
(NOꢀ3 )]. MS (FAB, m/z): 728 [CdL4]þ, 790
n
[CdL4(NOꢀ3 )]þ.
n
847 [Al2L1Cl5]þ.
AlL3Cl3$6H2O (2). Color: yellow. Anal. Calcd for C38N5O9H53Cl3Al:
Acknowledgements
C, 53.24; H, 6.18; N, 8.17. Found: C, 53.51; H, 5.90; N, 8.24%. Yield:
59.2%. IR (KBr, cmꢀ1): 1629 [
n
n
(C]N)imin]; 1602, 1457 [
n
(C]C) and
We thank Fundaça˜o para a Ciencia e a Tecnologia/FEDER (Por-
tugal/EU) (Project PTDC/QUI/66250/2006 FCT-FEDER), Xunta de
Galicia (Spain) (Project PGIDIT07PXIB209039PR) for financial sup-
port. C.N, A.M, R.B, J.L., and C.L. would like to thank the program
‘Joint Portuguese–Spanish Project 2007’ for the bilateral agreement
number 63/07(Portugal) / HP2006-0119 (Spain). C.N. thanks Xunta
de Galicia for her Maria Barbeito program pre-doctoral contract. E.B.
is grateful to Canterbury Christ Church University for financial
ˆ
(C]N)py]. MS (FAB, m/z): 765 [Al3L3Cl2]þ.
4.3.6. General procedure for complexes with the amine macrocycles
L2 and L4
The appropriate metal salt (0.02 mmol) in absolute ethanol
(5 mL) was added dropwise to a stirred solution of the ligand L2 or
L4 (0.02 mmol) in the same solvent (15 mL). The resulting mixture

6188
C. Nu´n˜ez et al. / Tetrahedron 65 (2009) 6179–6188
Cui, D. Org. Lett. 2005, 7, 899; (e) Royzen, M.; Dai, Z.; Canary, J. W. J. Am. Chem.
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support. J.L.C. and C.L. thank Xunta de Galicia for the Isidro Parga
Pondal Research program.
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