Selective and sensitive chromogenic detection of trivalent metal cations in water

Article abstract of DOI:10.1246/bcsj.20150416

An azopyridine derivative for the selective and sensitive chromogenic detection of trivalent metal cations in water is described.

Full text of DOI:10.1246/bcsj.20150416

Short Articles
OH HO
N
Selective and Sensitive Chromogenic
Detection of Trivalent Metal Cations
in Water
O
O
3
O
O
MsCl
Et
O
O
N
HO
MsO
N
3
NaH
1
2
4
NaNO
/ H+
2
Beatriz Lozano-Torres,1,2,3
Sameh El Sayed,1,2,3
Ana M. Costero,*1,3,4
Salvador Gil,1,3,4 Margarita Parra,1,3,4
Ramón Martínez-Máñez,*1,2,3
O
O
O
NH2
N
N
N
N
O
6
N
5
R. Martínez-Máñez
Figure 1. Schematic representation of the pathway fol-
lowed to synthesize probe 6.
and Félix Sancenón1,2,3
presented in several proteins, cofactors and enzyme active
sites and its poisoning is linked with a variety of neurologic,
dermatologic, cardiovascular, and carcinogenic effects.
1Centro de Reconocimiento Molecular y Desarrollo
Tecnológico (IDM), Unidad Mixta Universidad Politécnica
de Valencia-Universidad de Valencia, Spain
8
All the above-mentioned facts have boosted, in the last years,
the synthesis of chromo-fluorogenic chemosensors able to selec-
2Departamento de Química, Universidad Politécnica de
9­13
tively detect the presence of trivalent metal cations.
In spite
Valencia, Camino de Vera s/n, 46022, Valencia, Spain
3CIBER de Bioingeniería, Biomateriales y Nanomedicina
of this interest, the vast majority of the reported examples
worked in organic solvents limiting applicability in real bio-
logical and environmental media. As far as we know, only two
examples of probes for trivalent metal cations able to display
(
CIBER-BBN)
4Departamento de Química Orgánica, Facultad de Ciencias
Químicas, Universidad de Valencia, Doctor Moliner 50,
1
4,15
sensing features in pure water have been reported to date.
Bearing in mind the above-mentioned facts and our interest
46100 Burjassot, Valencia, Spain
1
6
in the design of molecular and material-based optical probes,
E-mail: rmaez@qim.upv.es, ana.costero@uv.es
Received: December 3, 2015; Accepted: January 15, 2016;
Web Released: January 22, 2016
we report herein the synthesis, characterization, and coordina-
tion behavior of an azopyridine chemosensor 6 which is able to
chromogenically sense trivalent metal cations in pure water.
The synthesis of 6 is depicted in Figure 1. In the first step,
2
-methoxyethanol (1) was mesylated with mesyl chloride
Abstract
yielding derivative 2. Then, the Williamson ether synthesis was
used to prepare the oligoethylene glycol derivative 4. Finally,
chemosensor 6 was obtained through a diazotization reaction
between 4 and the diazonium salt of 4-aminopyridine (5). The
overall yield of 6 was 21% (see Supporting Information for
details). The synthesis of compound 6 was slightly modified
from a previously described protocol. 6 was composed of
an azopyridine scaffold (as signaling reporter) and two oligo-
ethylene glycol chains which were included in the molecule
to impart water solubility to the probe. Chemosensor 6 could
potentially interact with metal cations due to the presence of
four nitrogen atoms in its structure.
An azopyridine derivative for the selective and sensitive
chromogenic detection of trivalent metal cations in water is
described.
The application of supramolecular concepts for the synthesis
and characterization of chromo-fluorogenic chemosensors for
transition metal cations is a well stablished area in the field
of supramolecular chemistry. Most of the reported examples
use the “binding site-signaling subunit” approach and have
been developed for the colorimetric or fluorimetric detection of
1
7
1
2
alkaline, alkaline-earth, or transition metal cations. Inside this
last type of cations, those containing three positive charges are
especially appealing as they are involved in many biological
Water solutions of 6 at pH 7.0 showed an intense orange
color due to the presence of a broad absorption band centered
at 470 nm (¾ = 5.69 © 10 M cm ) with a shoulder at 545
3
3+
3
¹1
¹1
and environmental processes. In this respect, Fe is a cofactor
of the electron transport system and it is present in a large
3
¹1
¹1
nm (¾ = 3.02 © 10 M cm ). The UV­visible behavior of 6
4
3+
+
+
+
number of enzymes and proteins. On the other hand, Al is a
common water pollutant and its accumulation could lead to a
wide range of diseases such as Alzheimer, Parkinson, enceph-
upon addition of alkaline (Li , Na , and K ), alkaline-earth
(Mg and Ba ), and transition metal (Co , Cu , Ni
2+
2+
2+
2+
2+
,
Cd +, Zn2+, Al3+, Ga , In , Fe , and As ) cations was
tested. The obtained results are showed in Figure 2. As seen,
only addition of trivalent cations were able to induce a
remarkable color change from orange to violet allowing the
naked eye detection of these triple charged species. This selec-
tivity is tentatively ascribed to the high polarizing power of
these small and highly charged cations, when compared with
other monovalent and divalent cations.
2
3+
3+
3+
3+
alopathy, and osteoporosis.5 Similar to Al , Ga can be
3+
3+
present in water, fruits and vegetables in small traces, and
6
it could form derivatives that cause respiratory problems.
Moreover, indium has been reported to damage heart, kidney,
and liver. Additionally, the derivative indium pentetreotide has
7
been used as a treatment for cancer that has spread to bones.
3+
Finally, As is highly toxic due to its affinity for thiols
498 | Bull. Chem. Soc. Jpn. 2016, 89, 498–500 | doi:10.1246/bcsj.20150416
© 2016 The Chemical Society of Japan

1
0
0
0
0
0
0
0
0
0
0
,0
,9
,8
,7
,6
,5
,4
,3
,2
,1
,0
8
equiv
0
equiv
Figure 2. Color changes observed for water solutions of 6
(
300
400
500
λ/nm
600
700
1.0 © 10 4 mol L ) at pH 7.0 upon addition of 1 equiv of
¹
¹1
selected metal cations.
Figure 4. UV­visible profile of the titrations of chemosen-
sor 6 (1.0 © 10¹4 mol L ) in water at pH 7.0 upon addi-
tion of increasing quantities of As cation (0­8 equiv).
0
0
,16
,14
¹1
1,0
0,8
0,6
0,4
0,2
0,0
0,12
3+
Al
0,10
0,08
0,06
0,04
3+
0,02
,00
0,02
0
Table 1. Complexation constants and limits of detection for
6 with trivalent cations
-
0
,0 0,2 0,4 0,6 0,8 1,0
8 equiv
0 equiv
χHost
Cation
log K
Limit of detection/¯M
3
+
Al
In
6.21 « 0.04
5.04 « 0.06
4.99 « 0.04
2.42 « 0.04
5.16 « 0.06
8.95
10.2
11.2
12.6
6.44
3
+
3
+
Ga
3+
Fe
3
+
As
2
50 300 350 400 450 500 550 600 650 700
/nm
λ
centered at 474 nm together with a marked decrease of the
absorption at 545 nm). The appearance of the red-shifted
Figure 3. UV­visible profile of the titrations of chemo-
3+
absorption suggested also that As cation interacted with the
acceptor part of chemosensor 6. The new band centered at
¹4
¹1
sensor 6 (1.0 © 10 mol L ) in water at pH 7.0 upon
3+
addition of increasing quantities of Al
cation (0­8
3
+
4
74 nm, which appeared at higher As concentrations, was
equiv). Inset: Job’s plot for the complexation between 6
and Al3+ cation determined by UV­vis measurements in
ascribed to a coordination of the cation with the 1:1 stoichi-
ometry complex previously formed.
3
+
¹4
¹1
water at pH 7.0 with [6] + [Al ] = 1.0 © 10 mol L
.
From UV­visible titrations the limits of detection (LOD) of
3+
3+
3+
3+
3+
Having assessed the highly selective response of 6 toward
trivalent metal cations, the sensitivity of the probe was studied
by monitoring UV­visible changes in water at pH 7.0 upon
6 for Al , Fe , Ga , In , and As cations were evaluated
(Table 1). The LODs obtained are in the ¯M range and are
similar to those calculated for other recently published
chromogenic probes for trivalent cations (Table SI-1 in
3
+
3+
3+
3+
the addition of increasing quantities of Fe , Al , Ga , In
,
3+
9­15
and As . The UV­visible and emission profiles obtained in
Supporting Information).
3+
3+
3+
3+
the presence of Fe , Al , Ga , and In cations were quite
similar and, as an example, the complete set of spectra obtained
Moreover, in order to determine the binding stoichiometry
between 6 and the trivalent metal cations, Job’s plots were
performed. As an example the inset of Figure 3 shows the Job’s
3
+
for 6 and Al is shown in Figure 3.
Upon addition of increasing amounts of Al3 (0­8 equiv) to
water solutions of 6 at pH 7.0 the absorbance at 470 nm de-
creased with the simultaneous growth of a new red-shifted
absorption band centered at 545 nm with a clear isosbestic
point at 458 nm. The appearance of a red-shifted absorption
suggested that Al cation interacted with the acceptor part of
chemosensor 6, namely the pyridine heterocycle or the diazo
group.
However, the chromogenic response observed with As3+
cation is slightly different and no isosbestic points were ob-
served in the set of spectra (Figure 4). Addition of increasing
+
plot determined for Al that clearly shows the formation of
3+
1:1 chemosensor-cation species. 1:1 stoichiometries were also
3
+
3+
3+
determined for 6 with Fe , Ga , and In (data not shown).
3+
In the case of As only the set of spectra obtained at low metal
cation concentrations (when only 1:1 stoichiometry complex
was formed) was used for the estimation of the stability
constant. Based in the Job’s plots the corresponding stability
constants for the formation of [M(6)] complexes were deter-
mined using the HypSpec software (V 1.1.18) and adjusting
the data to the equilibrium equation:
3+
3
+
3
þ
þ L ꢀ ½MðLÞꢀ3þ
M
ð1Þ
3+
quantities of As cation (0­0.5 equiv) to water solutions of 6
at pH 7.0 induced a progressive decrease of the absorbance of
the band centered at 470 nm with the subsequent appearance
of new red-shifted absorption (at 545 nm). However, addition
The estimated values of log K obtained using UV­visible
titration profiles are shown in Table 1.
Probe 6 contains four nitrogen atoms (one in the aniline
fragment, two in the azo moiety and one in the pyridine
3+
of higher As amounts induced the appearance of a new band
Bull. Chem. Soc. Jpn. 2016, 89, 498–500 | doi:10.1246/bcsj.20150416
© 2016 The Chemical Society of Japan | 499

Hb
Hb
Ha
Ha
References
Hd
N
Hc
Hc
R
N
R
N
N
2 2 2 3
R = (CH CH O) CH
1
2
B. Valeur, I. Leray, Coord. Chem. Rev. 2000, 205, 3.
a) M. Formica, V. Fusi, L. Giorgi, M. Micheloni, Coord.
Hd
Chem. Rev. 2012, 256, 170. b) E. M. Nolan, S. J. Lippard, Chem.
Rev. 2008, 108, 3443.
Hd
Hc Hb
Ha
6
6
+ 1.4 equiv Al3+
3
11805.
4
S. Paul, A. Manna, S. Goswami, Dalton Trans. 2015, 44,
Hd
Hd
Hc Hb
Hc Hb
Ha
Ha
+ 0.7 equiv Al3+
+ 0.2 equiv Al3+
S. Goswami, K. Aich, S. Das, A. K. Das, D. Sarkar, S.
Panja, T. K. Mondal, S. Mukhopadhyay, Chem. Commun. 2013,
49, 10739.
6
5
a) V. B. Gupta, S. Anitha, M. L. Hegde, L. Zecca, R. M.
Hd
Hb
Hc
Ha
Garruto, R. Ravid, S. K. Shankar, R. Stein, P. Shanmugavelu,
K. S. J. Rao, Cell. Mol. Life Sci. 2005, 62, 143. b) T. P. Flaten,
Brain Res. Bull. 2001, 55, 187.
6
6
a) R. E. Caffrey-Nolan, K. L. McCoy, Toxicol. Appl.
Pharmacol. 1998, 151, 330. b) S. M. Kennedy, D. C. Walker, A. S.
Belzberg, J. C. Hogg, J. Nucl. Med. 1985, 26, 1195.
Figure 5. 1H NMR shifts of the aromatic protons of
chemosensor 6 in the presence of increasing quantities of
Al in D2O.
7
a) G. Gabbiani, H. Selye, B. Tuchweber, Br. J. Pharmacol.
962, 19, 508. b) J. R. Buscombe, M. E. Caplin, A. J. W. Hilson,
J. Nucl. Med. 2003, 44, 1.
1
3+
8
a) A. S. Akinrinde, E. Olowu, A. A. Oyagbemi, O. T.
heterocycle) that could potentially interact with trivalent metal
cations. In order to establish the coordination mode H NMR
Omobowale, Pharmacogn. Res. 2015, 7, 268. b) N. V. Solenkova,
J. D. Newman, J. S. Berger, G. Thurston, J. S. Hochman, G. A.
Lamas, Am. Heart J. 2014, 168, 812.
1
studies of solutions of 6 in D2O upon addition of increasing
3
+
quantities of Al cation were carried out. The most remarkable
changes were observed in the signals of the aromatic zone
9
L. E. Santos-Figueroa, A. Llopis-Lorente, S. Royo, F.
Sancenón, R. Martínez-Máñez, A. M. Costero, S. Gil, M. Parra,
ChemPlusChem 2015, 80, 800.
(Figure 5). Protons of the 1,4-disubstituted aniline ring in 6
appeared as doublets centered at 7.02 (Ha) and 7.90 ppm (Hb)
whereas the pyridine protons appeared, also as doublets, at
10 A. Barba-Bon, A. M. Costero, S. Gil, M. Parra, J. Soto, R.
Martínez-Máñez, F. Sancenón, Chem. Commun. 2012, 48, 3000.
11 X. Zhao, G. Yin, D. Jin, X. Yan, Y. Li, L. Chen,
J. Fluoresc. 2015, 25, 327.
7
.68 (Hc) and 8.68 ppm (Hd). As seen in the family of spectra
3+
shown in Figure 5, addition of increasing quantities of Al
1
2
C. Marín-Hernández, L. E. Santos-Figueroa, M. E.
cation induced moderate downfield shifts of Ha and Hd pro-
tons. However, the most remarkable changes were observed for
Hb and Hc protons that suffered downfield shifts of ca. 0.1 and
Moragues, M. M. M. Raposo, R. M. F. Batista, S. P. G. Costa,
T. Pardo, R. Martínez-Máñez, F. Sancenón, J. Org. Chem. 2014,
7
9, 10752.
0
.4 ppm, respectively. We tentatively assigned these changes to
3
+
13 H. Kim, K. B. Kim, E. J. Song, I. H. Hwang, J. Y. Noh, P.-G.
the interaction of Al cation with the azo group present in
6
titration of 6 with As cation).
Kim, K.-D. Jeong, C. Kim, Inorg. Chem. Commun. 2013, 36, 72.
S. Tao, Y. Wei, C. Wang, Z. Wang, P. Fan, D. Shi, B. Ding,
J. Qiu, RSC Adv. 2014, 4, 46955.
S. Samanta, S. Goswami, A. Ramesh, G. Das, J. Photo-
chem. Photobiol., A 2015, 310, 45.
See for example: a) L. Pascual, I. Baroja, E. Aznar, F.
1
(Figure SI-5 in Supporting Information for the H NMR
1
4
3
+
In summary, we have reported the preparation of a simple
chromogenic probe, based on a azopyridine derivative, for the
1
5
colorimetric detection of Al3 , Fe , Ga , In , and As over
mono- and divalent cations in pure water with LOD in the ¯M
range. In the presence of trivalent metal cations the chemo-
sensor was able to display a remarkable color change from
orange to violet clearly visible to the naked eye. This is one of
the few reported examples able to optically detect trivalent
metal cations in pure water.
+
3+
+3
3+
3+
1
6
Sancenón, M. D. Marcos, J. R. Murguía, P. Amorós, K. Rurack, R.
Martínez-Máñez, Chem. Commun. 2015, 51, 1414. b) S. El Sayed,
M. Milani, M. Licchelli, R. Martínez-Máñez, F. Sancenón, Chem.®
Eur. J. 2015, 21, 7002. c) M. E. Moragues, A. Toscani, F. Sancenón,
R. Martínez-Máñez, A. J. P. White, J. D. E. T. Wilton-Ely, J. Am.
Chem. Soc. 2014, 136, 11930. d) L. E. Santos-Figueroa, C.
Giménez, A. Agostini, E. Aznar, M. D. Marcos, F. Sancenón, R.
Martínez-Máñez, P. Amorós, Angew. Chem., Int. Ed. 2013, 52,
Financial support from the Spanish Government (Project
MAT2012-38429-C04), the Generalitat Valencia (Project
PROMETEOII/2014/047) and the CIBER de Bioingeniería,
Biomateriales y Nanomedicina (CIBER-BBN) is gratefully
acknowledged.
1
3712. e) M. Oroval, E. Climent, C. Coll, R. Eritja, A. Aviñó, M. D.
Marcos, F. Sancenón, R. Martínez-Máñez, P. Amorós, Chem.
Commun. 2013, 49, 5480. f) E. Climent, D. Gröninger, M. Hecht,
M. A. Walter, R. Martínez-Máñez, M. G. Weller, F. Sancenón, P.
Amorós, K. Rurack, Chem.®Eur. J. 2013, 19, 4117.
Supporting Information
17 N. Mas, A. Agostini, L. Mondragón, A. Bernardos, F.
Sancenón, M. D. Marcos, R. Martínez-Máñez, A. M. Costero, S.
Gil, M. Merino-Sanjuán, P. Amorós, M. Orzáez, E. Pérez-Payá,
Chem.®Eur. J. 2013, 19, 1346.
Full experimental details, compound characterization, and
selected spectra for key compounds. This material is available
on http://dx.doi.org/10.1246/bcsj.20150416.
500 | Bull. Chem. Soc. Jpn. 2016, 89, 498–500 | doi:10.1246/bcsj.20150416
© 2016 The Chemical Society of Japan