Ascorbic acid-based quinoxaline derivative as a chromogenic chemosensor for Cu2?+

Article abstract of DOI:10.1016/j.inoche.2016.05.019

Detection of cationic species represents an important field due to its importance in biological and environmental processes. This communication shows the synthesis and application of an ascorbic acid-based quinoxaline derivative (1) in the colorimetric de

Full text of DOI:10.1016/j.inoche.2016.05.019

Inorganic Chemistry Communications 70 (2016) 71–74
Contents lists available at ScienceDirect
Inorganic Chemistry Communications
journal homepage: www.elsevier.com/locate/inoche
Short Communication
Ascorbic acid-based quinoxaline derivative as a chromogenic
chemosensor for Cu2+
Lilian C. da Silva a, Erivaldo P. da Costa a, Gutto R.S. Freitas a, Miguel A.F. de Souza a, Renata M. Araújo a,
Vanderlei G. Machado b, Fabrício G. Menezes a,
⁎
a
Química Biológica e Quimiometria, Instituto de Química, Universidade Federal do Rio Grande do Norte, Natal, RN 59072-970, Brazil
Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Detection of cationic species represents an important field due to its importance in biological and environmental
Received 26 February 2016
Accepted 16 May 2016
Available online 20 May 2016
processes. This communication shows the synthesis and application of an ascorbic acid-based quinoxaline deriv-
ative (1) in the colorimetric detection of Cu2+ against several other cationic species, including Sr2+, Fe2+, Pb2+
,
Mn2+, Mg2+, Ni2+, Zn2+, Sn2+, Hg2+, Ca2+, Ba2+, Co2+, Cr3+, Al3+, and Fe3+. Based on experimental and the-
oretical results, a 1:2 binding model involving 1 and Cu2+ is proposed.
© 2016 Elsevier B.V. All rights reserved.
Keywords:
Quinoxaline
Naked-eye detection
Chromogenic chemosensor
Copper detection
The development of molecular and supramolecular strategies for the
recognition and detection of cationic species represents a field of in-
creasing importance in recent years [1]. In this context, the study of
chromogenic chemosensors for these analytes is attractive due to the
fact that the analysis procedures are simple and require low cost, with
naked-eye detection also being possible [2–4]. Copper (II) ions are one
of the main target analytes with relevance to be detected, since the re-
ferred metal is highly abundant in nature and essential to many biolog-
ical processes; on the other hand, its abnormal levels may lead to several
pathologies [5–8].
A wide range of quinoxaline derivatives has been reported in the
literature due to their relevant biological activity [9] and applications
in technological fields [10]. In addition, quinoxalines are found as inter-
esting nitrogenated ligands for coordination chemistry [11,12]. Tradi-
tionally, the synthesis of 2,3-disubstituted quinoxalines proceeds
through Brønsted or Lewis acid-catalyzed condensation of aromatic
o-diamines and α-diketones [13]. Based on this synthetic strategy,
there are several investigations reported in the literature concerned
with reactions of dehydro-L-ascorbic acid and o-phenylenediamine,
and an interesting aspect in these processes is related with the possi-
bility of different products mainly depending on the ratio of the reac-
tant and of the experimental conditions [14–21]. For instance, one pot
procedure involving mixing an equimolar amount of L-ascorbic acid
and 1,4-benzoquinone, followed by the addition of two equivalents of
o-phenylenediamine, leads to the formation of N-(2-aminophenyl)-3-
[(1S,2S)-1,2,3-trihydroxy-propyl]quinoxaline-2-carboxamide (1), as
presented in Scheme 1 [14,15].
Although quinoxaline derivative 1 has been known since 1964 [16],
this compound is surprisingly marginally reported in literature. A quick
look at the molecular structure of compound 1 reveals the presence
of eight Lewis basic sites from primary aniline, amide, quinoxaline and
hydroxyl groups, suggesting an attractive design to be applied in coordi-
nation chemistry. In this context, we report herein the use of ascorbic
acid-based quinoxaline 1 as a cationic chromogenic chemosensor.
More specifically, we demonstrate that compound 1 in methanol is
very selective for naked-eye and quantitative detection of Cu2+ be-
tween several utilized cations.
Compound 1 was easily obtained according to the literature
(Scheme 1) [14,15], from low cost reactants starting from L-ascorbic
acid in 72% yield, and spectroscopic data were in full agreement to the
proposed structure [22]. NMR characterization of compound 1 was re-
ported only in 2014, but not properly detailed [15], such as for data ob-
tained from bidimensional analysis, which is found to be very relevant
due to the complexity of the structural nature of the referred ligand, in-
cluding chirality aspects. All NMR spectra related to compound 1 are
presented here in the Supplementary Material (Figs. S1–S4). Fig. S4
(Supplementary Material) shows the experimental 1JH,C–HSQC spec-
trum of compound 1. Quinoxaline hydrogens are downfield in relation
to a substituted phenyl ring. This is a consequence of the combination
of the electron deficient nature of the heterocyclic unit, which is even
increased due to its direct connectivity to the carbonyl group, with the
⁎
Corresponding author.
E-mail address: fabricio@quimica.ufrn.br (F.G. Menezes).
http://dx.doi.org/10.1016/j.inoche.2016.05.019
1387-7003/© 2016 Elsevier B.V. All rights reserved.

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L.C. da Silva et al. / Inorganic Chemistry Communications 70 (2016) 71–74
Scheme 1. One pot synthesis of compound 1.
electron donation ability of both nitrogen atoms of the amine and amide
groups attached to the phenyl ring. In the aliphatic moiety of the molec-
ular structure, the diastereotopic hydrogens of the methylene group ap-
pear as two multiplets at the higher field region of the spectrum, as a
consequence of the two stereogenic centers in the ligand.
immediately after the addition of 1 (Fig. 1a), and this behavior is consis-
tent with the results obtained from UV–vis analysis (Fig. 1b–c). All data
in Fig. 1 were acquired 5 min after the mixture of the reagents. A new
band emerges in the visible region with maximum absorbance at
416 nm, suggesting a formation of a coordination complex between 1
and Cu2+ (Fig. 1b–c).
Quinoxaline 1 (1 × 10−4 mol L−1) was added to solutions containing
5 equivalents of several cationic species (Cu2+, Sr2+, Fe2+, Pb2+, Mn2+
,
Spectrophotometric titration was performed in order to investigate
the stoichiometry of this interaction and it was found that absorbance
of the complex between ligand 1 (1 × 10−4 mol L−1) and Cu2+ was en-
hanced as the concentration of Cu2+ ion increased until saturation at
approximately 2 × 10−4 mol L−1, suggesting a 1:2 1:Cu2+ stoichiome-
try (Fig. 2). In attempt to verify sensibility aspects, another experiment
using 0.5 μmol L−1 of chemosensor 1 toward 10 equivalents of each
metal was performed and Cu2+ selectivity could be demonstrated by
UV–vis spectroscopy, through with an increase in the absorbance at
416 nm. The selectivity of compound 1 for Cu2+ in the presence of
different metal ions was investigated using UV–vis analysis of solutions
containing compound 1 together with one equivalent of Cu2+ and an
equimolecular amount of another cation (Fig. 3). A small increase in
the absorbance at 416 nm was found when Mg2+ and Pb2+ compete
with Cu2+. On the other hand, Al3+ and Sn2+ lead to a substantial de-
crease in the absorbance at 416 nm. This is not an unexpected result
since there are several electronic donor sites in compound 1 able
to complex cationic species. Data suggest that those metal ions are
complexing with 1 in a different binding site than the site responsible
for the complexation of Cu2+. Those metal ions would be responsible
for reinforcing or weakening the interaction of Cu2+ with 1, leading to
the observed results.
Mg2+, Ni2+, Zn2+, Sn2+, Hg2+, Ca2+, Ba2+, Co2+, Cr3+, Al3+, and Fe3+
)
in methanol. Only the solution containing Cu2+ changes its color
The infrared spectra of compound 1 and its coordination complex
were compared in an attempt to understand the chemical nature of
Fig. 1. Methanolic solutions of compound 1 (1.0 × 10−4 mol L−1) in absence and in
presence of Cu2+, Sr2+, Fe2+, Pb2+, Mn2+, Mg2+, Ni2+, Zn2+, Sn2+, Hg2+, Ca2+, Ba2+
,
Co2+, Fe3+, Cr3+ and Al3+ (5.0 × 10−4 mol L−1): (a) naked-eye detection of Cu2+
;
Fig. 2. Corresponding titration curve based on addition of Cu2+ (0 to 5 equivalents) to
solutions of compound 1 (1.0 × 10−4 mol L−1). All spectra were obtained 5 min after
the addition of the reagents.
(b) UV–vis spectra of resulting solutions; (c) changes in the absorbances at 416 nm. All
spectra were obtained 5 min after the addition of the reagents.

L.C. da Silva et al. / Inorganic Chemistry Communications 70 (2016) 71–74
73
Fig. 3. Normalized absorbances at 416 nm for equimolar mixtures of ligand 1, Cu2+ and
one more metal ion, both 1.0 × 10−4 mol L−1 in methanol. Normalization was based on
absorbance of the solution containing only compound 1 and Cu2+ (black bar).
Fig. 5. Proposed structure for the bi-metallic complex obtained from interaction of ligand 1
and two equivalents of CuCl2.
the interactions between quinoxaline derivative 1 and Cu2+ ion (Fig. 4).
Data strongly suggest coordination through carbonyl oxygen, since the
band attributed to C_O bond stretching shifts from 1650 cm−1 in the
free ligand to 1627 cm−1 in the coordination complex, and this shift
to red is coherent with previous data in the literature [23,24]. In addi-
tion, a change in the position of the band relative to C_N bond, from
1532 cm−1 to 1485 cm−1, suggests a quinoxaline nitrogen also partici-
pating in coordination to the metal ion.
The M06-L/6-31G(d)//PM6 (DFT//semi-empirical combined method
[25,26], see details in Supplementary Material) calculations have been
performed to support the evidence obtained from spectrophotometric
titration, which suggests a complex formed by ligand 1 and two equiv-
alents of CuCl2. Firstly, a scanning of several conformations was per-
formed to indicate the more favorable structure of compound 1 (see
Fig. S5 in Supplementary Material). Afterwards, optimization calcula-
tions were performed to find a minimum structure for the bi-metallic
complex. Fig. 5 shows the more thermodynamically favorable com-
plexation structure obtained. The equilibrium of this reaction was
found to be slightly thermodynamically unfavorable (+6.0 kcal mol−1).
The following coordination sites were found for the interaction of ligand
1 with two copper ions: (1) copper to a nitrogen of the quinoxaline unit
and the oxygen of the carbonyl group, leading to distorted planar square
geometry; (2) copper to the another quinoxaline nitrogen and an oxy-
gen of the hydroxyl group, resulting in distorted tetrahedral geometry.
In both cases, the complexation led to five-membered metallocyclic
structures. Experimental infrared data and theoretical results were
found to be in good agreement, particularly with respect to the bands
attributed to C_O bond stretching of the bi-metallic complex, which
were centered at 1627 cm−1 and 1617 cm−1 in the experimental and
theoretical spectra, respectively.
To summarize, compound 1 was easily obtained from ascorbic acid
and o-phenylenediamine. This compound is an efficient chromogenic
chemosensor in methanol for the detection of Cu2+ between several
other cationic species studied. Experimental data, in combination with
theoretical calculations, allowed for an evaluation of the selective
binding of quinoxaline 1 to Cu2+, suggesting the formation of a complex
exhibiting 1:2 ligand:metal stoichiometry. Due to the high relevance of
the development of selective chemosensors for ionic species [2,3,27],
we are currently working on additional studies involving interactions
of ligand 1 with cationic species, including synthetic transformations
on compound 1 in attempt to improve the recognition and sensing
ability of this system.
Acknowledgments
The authors give thanks for the financial support from the Brazilian
Conselho Nacional de Desenvolvimento Científico e Tecnológico
(CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
(CAPES), and Fundação de Apoio à Pesquisa do Rio Grande do Norte
(FAPERN, grant 005/2012), as well as UFRN and UFSC.
Appendix A. Supplementary data
Supplementary data associated with this article include experimen-
tal and theoretical procedures, NMR spectra and scanning of the more
stable energetic conformer of compound 1. These data can be found in
the online version at: http://dx.doi.org/10.1016/j.inoche. Supplementa-
ry data associated with this article can be found in the online version, at
http://dx.doi.org/10.1016/j.inoche.2016.05.019.
Fig. 4. Infrared spectra (1750 to 500 cm−1) of compound 1 (red line) and its copper
coordination complex (black line). (For interpretation of the references to color in this
figure legend, the reader is referred to the web version of this article.)

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L.C. da Silva et al. / Inorganic Chemistry Communications 70 (2016) 71–74
[17] X. Wu, Y. Diao, C. Sun, J. Yang, Y. Wang, S. Sun, Fluorimetric determination of ascor-
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