A two-channel molecular dosimeter for the optical detection of copper(II)

Article abstract of DOI:10.1039/b305456j

A cyclam-like macrocycle with an integrated push-pull chromophore selectively detects Cu²⁺ inclusion through both orange-to-yellow colour change and quenching of the green fluorescence.

Full text of DOI:10.1039/b305456j

A two-channel molecular dosimeter for the optical detection of
copper(II)†
Massimo Boiocchi,a Luigi Fabbrizzi,*b Maurizio Licchelli,b Donatella Sacchi,b Miguel Vázquezb and
Cristina Zampab
a Centro Grandi Strumenti, Università di Pavia, Cascina Cravino, I-27100 Pavia, Italy
b Dipartimento di Chimica Generale, Università di Pavia, via Taramelli 12, I-27100 Pavia, Italy.
E-mail: luigi.fabbrizzi@unipv.it; Fax: +39 0382 528544; Tel: +39 0382 507328
Received (in Cambridge, UK) 15th May 2003, Accepted 13th June 2003
First published as an Advance Article on the web 27th June 2003
A cyclam-like macrocycle with an integrated push-pull
chromophore selectively detects Cu2+ inclusion through
both orange-to-yellow colour change and quenching of the
green fluorescence.
the CuII–N(aniline) bond, 2.07 Å, is only slightly longer than
the three Cu2+–N(amine) bonds (average value: 2.00 ± 0.01 Å),
indicating the existence of a regular metal–ligand interaction.
Noticeably, the macrocycle adopts an unusual configuration for
metal complexes of cyclam and its derivatives. In particular, a
diastereoisomer of type trans-I is observed (with the sub-
stituents on the nitrogen atoms, hydrogens and 4-nitrophenyl all
above the N4 plane; nitrogen configuration R,S,R,S; notice that
the CuII centre stays on the same side, at 0.03 Å over the N4
plane). Such a configuration has been previously observed only
in the case of complexes of N,NA,NB,NÚ-tetra-substituted
cyclams, e.g. [Cu2+(Me4cyclam)Br]Br.5 Usually, diastereo-
isomers of type trans-III (R,S,S,R) are observed.6
On the basis of the structural evidence, it is possible to
account for the spectral features of the titration of 1 with Cu2+,
as illustrated in Fig. 1. On titration, the Cu2+ ion is fully chelated
by the tetra-aza ring of 1. Hence, the interaction of the metal
with the lone pair of the aniline nitrogen modifies the intensity
of the dipole of the chromophore, raising the energy of the
There exists compelling interest in the design of receptors
capable of recognising cations and anions, and of communicat-
ing recognition through a visual signal. In the case of metal ions,
a convenient procedure involves the incorporation of a push–
pull chromophore into a multidentate ligand: coordinative
interaction with a given metal may alter the intensity of the
dipole of the chromophore, thus modifying the energy of the
charge transfer transition and ultimately changing the colour.
Such a topic has been especially exploited for the colorimetric
detection of s block metal ions, by equipping crown ether
receptors with a variety of chromophores.1 On the other hand,
much less interest has been devoted to colorimetric sensors for
transition metals based on push–pull chromophores.
We describe here the design of two tetramine macrocycles
containing an incorporated push–pull chromophore, suitable for
interaction with 3d metal ions. In system 1, the classical
(4-nitrophenyl)amine fragment (yellow colour) is a part of the
cyclam ring, while in system 2 the macrocycle contains the
7-nitrobenzo[1,2,5]oxadiazol-4-ylamine chromophore, which
maintains the skeleton of 4-nitrophenylamine, but also pos-
sesses a condensed furazan ring (orange-red colour).
Metal inclusion was investigated by titrating an aqueous
solution of 1, adjusted to pH = 4.75 with acetate buffer, with an
aqueous standard solution of the metal salt and looking at colour
changes and modifications of the absorption spectrum. Inter-
esting results were observed in the case of Cu2+, whose gradual
addition induced (i) decolorisation of the yellow solution and
(ii) a decrease of the band at 386 nm and development of a new
band at 266 nm (see Fig. 1). Very significantly, the absorbance
at 386 nm stopped decreasing after the addition of 1 equiv. of
Cu2+ (see inset of Fig. 1), thus indicating the formation of a
Cu2+/1 adduct of 1 : 1 stoichiometry. On concentration of the
colourless solution, a violet solid precipitated, whose elemental
analysis corresponded to the formula [Cu2+(1)](ClO4)2. Re-
crystallisation of the complex salt from MeCN gave violet
crystals, which were investigated through X-ray diffraction
studies.‡
Fig. 1 Titration of an aqueous solution 1024
M in 1, buffered at pH = 4.75,
with a standard solution of Cu2+. Inset: absorbance at 386 nm vs. equivalents
of Cu2+ (n).
The ORTEP diagram of the [Cu2+(1)](ClO4)2 complex is
shown in Fig. 2. The Cu2+ ion is fully encircled by the tetra-aza
subunit of 1 according to a square geometry. More interestingly,
Fig. 2 ORTEP diagram of the [Cu2+(1)](ClO4)2 complex. Thermal
ellipsoids are at 50% probability. Selected bond lengths (Å) and angles (°):
Cu1–N1 2.067(5), Cu1–N2 2.006(6), Cu1–N3 1.996(5), Cu1–N4 2.005(6),
N1–Cu1–N2 94.1(2), N1–Cu1–N3 167.4(2), N1–Cu1–N4 87.2(2), N2–
Cu1–N3 87.1(3), N2–Cu1–N4 170.7(2), N3–Cu1–N4 93.7(3).
† Electronic supplementary information (ESI) available: additional figure
and synthesis of ligands 1 and 2. See http://www.rsc.org/suppdata/cc/b3/
b305456j/
1812
CHEM. COMMUN., 2003, 1812–1813
This journal is © The Royal Society of Chemistry 2003

charge transfer from the dialkylamine fragment to the nitro
group, with a consequent shift of the pertinent absorption band
from 386 to 266 nm (which makes colour disappear). After-
ward, analogous titration experiments were carried out with a
variety of metal ions, which included Mn2+, Fe2+, Fe3+, Co2+,
Ni2+, Zn2+ and Pb2+: in all cases, neither a colour change nor a
modification of the spectral features of 1 were observed,
indicating that the metal does not interact with the aniline group
of the chromophore and, presumably, with the tetra-aza
macrocycle. Lack of interaction may be due to thermodynamic
reasons. In particular, the presence of the aniline nitrogen atom
in the donor set reduces the donating tendencies of the
macrocycle, which is able to form a stable complex only with
the metal highest in the Irving–Williams series, i.e. Cu2+.
Lack of interference by the above mentioned metals was
further demonstrated by titrating with a standard Cu2+ solution
an aqueous solution containing 1 plus 10 equiv. of the
interfering metal: in all cases, the family of spectra and the
titration profile shown in Fig. 1 were not altered. Thus, 1 is able
to detect Cu2+ through the perceptible disappearance of its
yellow colour and through a distinct change of the spectrum. In
particular, the amount of Cu2+ in solution can be estimated from
the absorbance of the band at 266 nm, whose limiting value is
7185 mol21 L cm21. It has to be noted that the inclusion of the
Cu2+ ion within the macrocycle is not reversible.
Fig. 3 Spectrofluorimetric titration of an aqueous solution 2 3 1025
M in 2,
buffered to pH = 4.75, with a standard solution of Cu2+. On metal addition,
the emission band at 523 nm decreases and the green fluorescence is
quenched. Inset: fluorescence intensity at 523 nm vs. equivalents of Cu2+
(n).
For instance, Cu2+ is not removed from the poly-aza ring of
1, even after the addition of a large excess of strong acid, a
feature typically observed for the especially inert transition
metal cyclam complexes. Thus, 1 cannot be defined as a
molecular sensor, a feature which requires quick reversibility
and potential re-utilisation. It should be rather defined as a
dosimeter, i.e. an irreversible device, which progressively
accumulates the dose, each time adding up the signal, and
which, after extended use, has to be discarded.7
Fig. 4 Visual features of the interactions of metal ions with 1 (a, colour) and
2 (b, colour; c, fluorescence) in aqueous solution at pH = 4.75.
fluorescence. A sensor operating through both absorption and
emission has been reported by de Silva.8 Visual features of
systems 1 (colour) and 2 (colour and fluorescence) before and
after the addition of Cu2+ and selected metal ions are shown in
Fig. 4.
System 2 contains a more versatile chromogenic fragment in
which the increased p-delocalisation over all the unsaturated
molecular framework ensures (i) the occurrence of a charge
transfer transition of lower energy (orange-red colour), and (ii)
provides emissive behaviour (green fluorescence). In particular,
system 2, in an aqueous solution adjusted to pH = 4.75 with
CH3COO2/CH3COOH buffer, shows its low-energy band at
473 nm, with e = 28700 mol21 L cm21 and the solution
exhibits an orange-red colour. On addition of Cu2+, the solution
turns yellow, while the absorption spectrum is substantially
modified. In particular, the band at 473 nm decreases and
disappears, while bands at 323 nm and at 268 nm strengthen
(spectrum not shown; see ESI†). Also in the present case, the
spectrophotometric titration profile, e.g. absorbance at 323 nm
vs. equiv. of Cu2+, indicates 1 : 1 stoichiometry and formation
of the [Cu2+(2)]2+ tetra-aza-macrocyclic complex. As pre-
viously observed for system 1, addition of the same series of
transition metal ions causes neither colour change nor spectral
modification. Thus, the functionalised macrocycle 2 behaves as
an exclusive optical dosimeter for Cu2+, whose detection is now
visually signalled by a sharp orange-to-yellow colour change.
On the emission side, we observed that system 2, when
irradiated at either 470 nm or 356 nm (iso-absorbing point),
gives rise to a green fluorescence. The emission band of an
aqueous solution of 2 adjusted to pH = 4.75 is centred at 523
nm and results from the radiative decay of the charge transfer
excited state. On titration with Cu2+, the intensity of the
emission band progressively decreases, to be quenched after the
addition of 1 equiv. of metal. (see spectra in Fig. 3). Again, the
IF vs. equiv. plot indicates 1 : 1 stoichiometry (see inset of Fig.
3). Fluorescence quenching has to be ascribed to the occurrence
of either an electron transfer or an electronic energy transfer
involving the transition metal and the nearby excited fluor-
ophore. On the other hand, titration with other transition metal
ions does not affect emission, indicating no interference.
Thus, system 2 is a novel and unique dosimeter for copper(II),
which operates through two different channels: (i) the orange-
to-yellow colour change and (ii) the quenching of the green
This work was financially supported by the European Union
(RT Network Molecular Level Devices and Machines—
Contract HPRN-CT-2000–00029), and by MIUR (Progetto
‘Dispositivi Supramolecolari’).
Notes and references
‡ Crystal structure analysis. X-Ray diffraction data were collected from a
violet prismatic crystal ( ~ 0.9 3 0.4 3 0.3 mm) by means of an Enraf
Nonius Cad4 diffractometer. Crystal data of C16H27Cu1N5O2(ClO4)2: M =
583.87, T = 273 K, monoclinic P21/c (no. 14), a = 8.688(12), b =
13.153(5), c = 21.497(22) Å, b = 108.05(6)°, V = 2336(4) Å3, Z = 4, rcalc
=
1.660 g cm23, m 1.226 mm21, psi-scan empirical absorption
=
correction applied,2 0.617 and 0.707 min and max transmission factors, l =
0.7107 Å, omega scans, 2qmax = 52°, 6348 measured reflections, 4573
independent reflections (Rint = 0.0419), 3197 independent reflections with
IO > 2s(IO), 336 parameters refined, GOF 1.040, R1 = 0.0747 (IO
>
2s(IO)) and 0.1075 (all data), R2w = 0.1936 (IO > 2s(IO)) and 0.2154 (all
data), largest difference peak and hole 0.80 and 20.50 e Å23. Crystal
structure was solved by direct methods (SIR 97)3 and refined by full-matrix
least-squares procedures on F2 using all reflections (SHELXL 97).4 CCDC
203828. See http://www.rsc.org/suppdata/cc/b3/b305456j/ for crystallo-
graphic files in CIF or other electronic format.
1 J. P. Dix and F. Vögtle, Chem. Ber., 1980, 113, 457.
2 A. C. T. North, D. C. Phillips and F. S. Mathews, Acta Crystallogr., Sect.
A, 1968, 24, 351.
3 A. Altomare, M. C. Burla, M. Camalli, G. L. Cascarano, C. Giacovazzo,
A. Guagliardi, A. G. G. Moliterni, G. Polidori and R. Spagna, J. Appl.
Crystallogr., 1999, 32, 115.
4 G. M. Sheldrick, SHELX-97 (SHELXS 97 and SHELXL 97), Programs
for Crystal Structure Analyses, University of Göttingen, Germany,
1998.
5 G. Kickelbick, T. Pintauer and K. Matijaszwski, New J. Chem., 2002, 26,
462.
6 L. F. Lindoy, The Chemistry of Macrocyclic Ligand Complexes,
Cambridge University Press, Cambridge, UK, 1989.
7 The first definition of ‘chemodosimeter’ was in M. Y. Chae and A. W.
Czarnik, J. Am. Chem. Soc., 1992, 114, 9704.
8 A. P. De Silva, H. Q. Gunaratne, H. Q. Nimal and M. Linch, J. Chem.
Soc., Perkin Trans. 2, 1995, 685.
CHEM. COMMUN., 2003, 1812–1813
1813