Corroles: Synthesis, functionalization and application as chemosensors

Article abstract of DOI:10.1002/open.201402001

Corroles exhibit rich spectroscopic features such as high molar extinction coefficients and fluorescence quantum yields. The core can accommodate various metal ions, which can act as active centers, and the periphery can be functionalized to enhance bindi

Full text of DOI:10.1002/open.201402001

DOI: 10.1002/open.201402001
Corroles: Synthesis, Functionalization and
Application as Chemosensors
Carla I. M. Santos*[a]
Awarding Institute: Universidade de Aveiro (Portugal)
Date Awarded: December 13, 2013
Supervisors: Prof. Dr. Maria da GraÅa de Pinho Morgado Silva Neves, Prof. Dr. Maria do Amparo Ferreira
Faustino, and Prof. Dr. Carlos Lodeiro EspiÇo
In recent years, the design and development of new fluorescent chemosensors has received great at-
tention due to its important applications in fields such as materials sciences, biomedical analysis, envi-
ronmental sciences and analytical chemistry, where molecular probes are often useful tools for moni-
toring relevant analytes either in vitro or in vivo. According to the literature a fluorescent chemosensor
is obtained by merging two fundamental moieties: the recognition site (receptor) and the signaling
source (fluorophore). Through the control of these two moieties it is possible to design a specific fluo-
rescent chemosensor for analytical sensing. However, to provide an efficient detection, these units
must have a high selectivity or specificity for the analyte and a stable luminescent signal.
Tetrapyrrolic macrocycles like porphyrins and analogues have useful properties to be considered as
fluorophores in this type of application. From the porphyrinoid family, corroles have merited special at-
tention in recent years since the discovery of facile methodologies to obtain synthetic triarylcorroles
and the corresponding metal complexes. These contracted macrocycles, that maintain the skeletal
structure of corrins, the aromaticity of porphyrins and that owe their name to the cobalt-chelating
corrin of vitamin B12 (Figure 1), exhibit rich spectroscopic features including: 1) high molar extinction
coefficients, 2) high fluorescence quantum yields, and 3) the corrole core can accommodate a broad
array of metal ions which in turn can act as active centers. In addition, corroles can be functionalized
at the structural periphery to enhance binding specificity. A corrole macrocycle is susceptible to react
at the inner nitrogen atoms, at the b-pyrrolic positions (2,3,7,8,12,13,17,18), at the meso-positions
(5,10,15) or at its aryl substituents.
Having these properties in mind, this dissertation focused on the synthesis of meso-triarylcorroles
and their functionalization for later use as chemosensors. The work was divided into five chapters. In
the first chapter, the general features of corroles, synthetic methodologies, the functionalization proce-
Figure 1. Structures of corrole, corrin and porphyrin core.
[a] C. I. M. Santos
University of Aveiro and BIOSCOPE Group
Monte de Caparica, Campus de Caparica
2829-516 Caparica (Portugal)
E-mail: csantos420@gmail.com
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/open.201402001.
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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License,
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Scheme 1. Reagents and conditions: a) i) GaCl3, py, reflux, ii) 1. HCl 36%, 2. NaHCO3(aq); b) Vilsmeier–Haack reagent; c) CH3PPh3Br, NaH in THF, RT, N2.
dures and the several potential applications of this kind of macrocycles is described. Additionally,
some considerations about chemosensors and the importance of analytes that will be evaluated are
also discussed. In the second chapter, the Wittig and Diels–Alder reactions were chosen as post-func-
tionalization procedures to apply to corroles. In this way, by the use of a Wittig reaction, the derivative
3-vinyl-5,10,15-tris(pentafluorophenyl)corrole was synthetized from the corresponding 3-formylcorrole.
The starting materials, 5,10,15-tris(pentafluorophenyl)corrole (1), 5,10,15-tris(pentafluorophenyl)-
corrolatogallium(III)(pyridine) (2), 3-formyl-5,10,15-tris(pentafluorophenyl)corrolatogallium(III) (3) were
synthesized according to procedures described in literature: the free base by condensation of pyrrole
with pentafluorobenzaldehyde using Gryko and Koszarna’s method, the gallium(III) complex by reflux-
ing corrole 1 in pyridine with GaCl3, and the 3-formylcorrole through a Vilsmeier–Haack reaction in-
volving corrole 2 (Scheme 1).
The reactivity of 3-vinyl-5,10,15-tris(pentafluorophenyl)corrole (4) as diene in Diels–Alder reactions
was also evaluated in the presence of the dienophiles 1,4-benzoquinone and 1,4-naphthoquinone
(Scheme 2). These studies afforded two Diels–Alder adducts (5 and 6) whose sensorial ability, as well
as of their precursors, was studied in solution in the presence of spherical (FÀ, BrÀ, ClÀ), linear (CNÀ)
À
and bulky (CH3COOÀ, H2PO4 ) biologically and environmentally relevant anions.
The 5,10,15-tris(pentafluorophenyl)corrole (1) showed to be the most sensitive macrocycle to the FÀ
(Figure 2). The addition of FÀ to 1 is responsible, in the absorption spectrum (Figure 2A), for a decrease
of the intensity of the band centered at 570 nm and for an increase at 606 nm, accompanied by a red-
shift from 606 nm to 619 nm (Dl=13 nm). An isosbestic point at 586 nm is also observed. Considering
the emission spectrum of 1 (Figure 2B), the titration with FÀ is responsible for an enhancement of in-
tensity of about 91% at 628 nm.
Scheme 2. Reagents and conditions: a) Reflux, toluene, N2; b) Reflux, toluene, N2.
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Figure 2. A) Spectrophotometric and B) spectrofluorimetric titration of compound 1 with the addition of FÀ in toluene. The
inset represents the absorption (A) and the emission intensity (B) as a function of [FÀ]/[1] at 570 nm, 619 nm for (A) and
628 nm, 680 nm for (B). ([1]=1ꢁ10À5 m, lexc =565 nm, T=298 K).
Although all derivatives interacted with this anion, the coordination of the corrole core with gallium-
(III) decreased their affinity for this anion, and consequently lower association constants were ob-
served.
In general, all compounds showed interaction with CNÀ. Two low-cost polymers based on polymeth-
ylmethacrylate (PMMA) and polyacrylamide were prepared and used in the detection of the anions FÀ
and CNÀ. The PMMA polymers doped with compounds 1 and 5 show a purple color, and a strong red
emission under UV lamp irradiation (l=365 nm) or when excited in the spectrofluorimeter at 565 nm.
However, the system did not show significant changes to the naked eye in the presence of the ana-
lytes. On the other hand, the acrylamide gel based on the same derivative 1 that in the absence of the
analyte was not emissive was able to switch on the emission after being submersed in a fluoride solu-
tion. The reason of this enhancement in emission intensity is probably due to the large pores in the
acrylamide gel that allow the entry of fluoride anions into the gel. The enhancement in the emission
intensity with time of submersion in a fluoride solution was performed with this polymer, and the
main results are shown in Figure 3. With cyanide a similar behavior was observed.
These studies were also extended to water samples. A polyacrylamide gel doped with corrole 1 was
introduced in water previously doped with different concentrations of cyanide, such as, 0, 0.5, 1.0, 2.0
and 4.0 ppm. Overall, corrole 1 in a solid support is able to detect a maximum of 1 ppm of cyanide in
water and a minimal amount of 70.0 ppb in water.
In the third chapter, the reactivity of the 3-vinylcorrole as a diene was extended to dimethyl acetyl-
enedicarboxylate as dienophile. This study afforded the two new corrole derivatives 7 and 8 (Figure 4).
The sensorial ability of the new macrocycles towards fluoride, cyanide, acetate and phosphate anions
was carried out by absorption and emission spectroscopy. Compound 7 showed to be colorimetric to
cyanide, where a change of color from green to colorless was visualized (Figure 5).
For in vivo applications, fluorescent chemosensors must to be water soluble. The change in the solu-
bility of the corrole macrocycle resulting from the insertion of coumarin-type units in its structure is
the subject of the fourth chapter. Two new corrole-coumarin derivatives were obtained from hetero-
Figure 3. A) Emission spectra of polyacrylamide gel doped with corrole 1 in the presence of FÀ as a function of time
(T=298 K, lexc =570 nm. B) PMMA film with 1 and C) polyacrilamide gel of 1 in the presence FÀ.
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Figure 4. Structures of the derivatives 7 and 8.
Figure 5. A) Spectrophotometric and B) spectrofluorimetric titration of compound 7 with the addition of CNÀ in toluene.
Diels–Alder reactions between the 3-vinylcorrole and o-quinone methides (o-QM) generated in situ
from Knoevenagel reactions of coumarins with paraformaldehyde (Scheme 3). The introduction of the
coumarin moiety conferred an unusual solubility of these conjugates in ethanol and in ethanol/water
(50:50) mixtures. The sensing ability of the resulting compounds was studied in the presence of differ-
ent anions. All corrole-coumarin conjugates interacted with cyanide anions. These sensorial studies
were extended to porphyrin-coumarin analogues. Porphyrin free-base conjugates were fully studied in
a mixture of ethanol/water (50:50), showing a colorimetric effect (color change from purple to yellow)
and an unprecedented selectivity for Hg2+. Having in mind the biological and environmental applica-
tion of these conjugates, non-expensive solid supports, like agarose and natural cellulose polymers
were developed. In the cellulose support material (filter paper) the colorimetric effect for Hg2+ reveals
a similar behavior as in solution.
The last chapter shows the sensorial ability of 5,10,15-tris(pentafluorophenyl)corrole (1) and of its
monoanionic species 1À towards Na+, Ca2+, Cu2+, Cd2+, Pb2+, Hg2+, Ag+, Al3+, Zn2+, Ni2+, Cr3+, Ga3+
,
Fe3+ metal ions in toluene and acetonitrile. The photophysical studies towards metal ions were carried
out by absorption and emission spectroscopy. These corroles showed to be selective and colorimetric
for Hg2+ (Figure 6). In addition, a new b-imine corrole was successful synthetized and further function-
Scheme 3. Reagents and conditions: a) Dioxane, reflux,
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Figure 6. A) Spectrophotometric and B) spectrofluorimetric titration of 1 with the addition of Hg2+ in acetonitrile. C) Normal-
ized fluorescence at 645 nm of corrole 1 with addition of 0.5 equivalents of metal ions in acetonitrile [(Na+, Ca2+, Cd2+
,
Cu2+, Pb2+, Hg2+, Ag+ and Al3+)=Mn+]; and picture with a color change from purple to green-blue with the addition Hg2+
in acetonitrile.
alized with 3-isocyanatopropyl-trimethoxysilane resulting in an alkoxysilane derivative. Knowing that
the incorporation of organic ligands in silica nanoparticles could improve the affinity, versatility and
sensitivity of the chromophores to the guests, the grafting of thealkoxysilane derivative with optically
transparent silica nanoparticles (SiNPs) was performed. The new, coated silica nanoparticles with cor-
role were studied in the presence of Cu2+, Hg2+ and Ag+ as metal ion probes. In the presence of Ag+
a change of color from green to yellow was observed.
The scientific work performed in this thesis allowed to obtain new knowledge on the corrole
chemistry. Currently it is known that is possible to introduce a vinyl group in a b-pyrrolic position of
the corrole core, through a Wittig reaction, and that the resulting b-vinylcorrole can participate as
diene in Diels–Alder reactions or as dienophile in the presence of reactive o-quinone methides.
In terms of sensorial behavior, the 5,10,15-trispentafluorophenycorrole showed to be highly sensitive
to fluoride anions, and exhibited the highest value of fluorescence quantum yield. It was also observed
that the insertion of a substituent at position 3 of the corrole unit leads to a decrease of the lumines-
cent quantum yield. This decrease can probably be attributed to conformation issues.
Although the coordination with gallium(III) and the functionalization at 3-position have originated
less emissive compounds, these derivatives have found application as colorimetric chemosensors and
as solid support sensors.
Keywords: chemosensors · corroles · cycloaddition reactions · nanoparticles
Publications arising from this work:
*
C. I. M. Santos, E. Oliveira, J. F. B. Barata, M. A. F. Faustino, J. A. S. Cavaleiro, M. G. P. M. S. Neves, C. Lodeiro, Inorg. Chim. Acta
2013, in press, DOI: 10.1016/j.ica.2013.09.049.
*
C. I. M. Santos, E. Oliveira, J. C. J. M. D. S. Menezes, J. F. B. Barata, M. A. F. Faustino, V. F. Ferreira, J. A. S. Cavaleiro,
M. G. P. M. S. Neves, C. Lodeiro, Tetrahedron 2013, in press, DOI: 10.1016/j.tet.2013.07.022.
*
C. I. M. Santos, E. Oliveira, J. F. Lodeiro, J. F. B. Barata, S. M. Santos, M. A. F. Faustino, J. A. S. Cavaleiro, M. G. P. M. S. Neves, C.
Lodeiro, Inorg. Chem. 2013, 52, 8564–8572.
*
C. I. M. Santos, E. Oliveira, J. F. B. Barata, M. A. F. Faustino, J. A. S. Cavaleiro, M. G. P. M. S. Neves, C. Lodeiro, J. Mater. Chem.
2012, 22, 13811–13820.
Received: February 27, 2014
Published online on April 11, 2014
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ChemistryOpen 2014, 3, 88 – 92 92