A new 3,5-bisporphyrinylpyridine derivative as a fluorescent ratiometric probe for zinc ions

Article abstract of DOI:10.1002/chem.201402270

A new 3,5-disubstituted pyridine with two porphyrin moieties was prepared through an efficient synthetic approach involving 2-formyl-5,10,15,20- tetraphenylporphyrin (1), piperidine, and catalytic amounts of [La(OTf) ₃]. 3,5-Bis(5,10,15,20-tetr

Full text of DOI:10.1002/chem.201402270

DOI: 10.1002/chem.201402270
Full Paper
&
Fluorescent Probes
A New 3,5-Bisporphyrinylpyridine Derivative as a Fluorescent
Ratiometric Probe for Zinc Ions
Nuno M. M. Moura,[a, b, c] Cristina NfflÇez,[b, c, d] SØrgio M. Santos,[e] M. Amparo F. Faustino,[a]
JosØ A. S. Cavaleiro,[a] Filipe A. Almeida Paz,[e] M. GraÅa P. M. S. Neves,*[a] JosØ Luis Capelo,[b, c]
and Carlos Lodeiro*[b, c]
Abstract: A new 3,5-disubstituted pyridine with two porphy-
rin moieties was prepared through an efficient synthetic ap-
proach involving 2-formyl-5,10,15,20-tetraphenylporphyrin
(1), piperidine, and catalytic amounts of [La(OTf)3]. 3,5-
Bis(5,10,15,20-tetraphenylporphyrin-2-ylmethyl)pyridine (2)
the appearance of a new band at 608 nm, which can be as-
signed to a metal-to-ligand charge transfer. The system was
able to quantify 79 ppb of Zn2+ and the theoretical calcula-
tions are in accordance with the stoichiometry observed in
solution. The gas-phase sensorial ability of compound 2 to-
wards all metal ions was confirmed by using MALDI-TOF MS
and in solid state by using polymeric films of polymethyl-
methacrylate (PMMA) doped with ligand 2. The results
showed that compound 2 can be analytically used to devel-
op new colorimetric molecular devices that are able to dis-
criminate between Hg2+ and Zn2+ in solid phase. The crystal
structure of ZnII complex of 3,5-bisporphyrinylpyridine was
unequivocally elucidated by using single-crystal X-ray diffrac-
tion studies.
was fully characterized and its sensing ability towards Zn2+
,
Cu2+, Hg2+, Cd2+, and Ag+ was evaluated in solution by ab-
sorption and fluorescence spectroscopy and in gas phase by
using matrix-assisted laser desorption/ionization (MALDI)-
TOF mass spectrometry. Strong changes in the ground and
excited state were detected in the case of the soft metal
ions Zn2+, Cd2+, Hg2+, and Cu2+. A three-metal-per-ligand
molar ratio was obtained in all cases and a significant ratio-
metric behavior was observed in the presence of Zn2+ with
sensors, and drugs.[1] In particular, porphyrins are considered
attractive candidates to be used as fluorescent and colorimet-
ric chemosensors due to their remarkable photophysical prop-
erties, such as large Stokes shifts and relatively long excitation
(>400 nm) and emission (>600 nm) wavelengths.[2,3] The high
interest on the development of probes that are able to detect
metal ions by fluorescence or colorimetric changes can be jus-
tified by the simplicity, quickness and the low detection limit
associated with optical techniques; moreover these inexpen-
sive methods are non-destructive and can be used in bio-imag-
ing.[4–7]
Introduction
The growing interest in tetrapyrrolic macrocycles, namely on
the development of new synthetic strategies to obtain new
functional derivatives, is related with their physicochemical fea-
tures that strongly encourage their application in several
fields; indeed, porphyrins are used as catalysts, advanced bio-
mimetic models for photosynthesis, new electronic materials,
[a] Dr. N. M. M. Moura, Prof. M. A. F. Faustino, Prof. J. A. S. Cavaleiro,
Prof. M. G. P. M. S. Neves
Department of Chemistry and QOPNA, University of Aveiro
Campus de Santiago, 3810-193 Aveiro (Portugal)
E-mail: gneves@ua.pt
The detection of the soft metal ions such as zinc(II) and cop-
per(II) are of particular interest due to their significant func-
tions on biological and environmental fields.[8–11] Other impor-
tant metal ions that merit to be studied are mercury(II) and
cadmium(II), due to their high toxicity for living organisms,[12]
being the selective detection of these metal ions of significant
importance for environmental and health-related issues.[13–16]
Most of the work using porphyrins as chemosensors in the
detection of metal ions are based on macrocyles functionalized
with adequate binding units in meso positions,[17] and as far as
we know much less attention is being given to porphyrins that
are b-functionalized.[18]
[b] Dr. N. M. M. Moura, Dr. C. NfflÇez, Prof. J. L. Capelo, Prof. C. Lodeiro
BIOSCOPE Group, REQUIMTE, Chemistry Department
Faculty of Science and Technology, University NOVA of Lisbon
2829-516, Monte da Caparica (Portugal)
E-mail: cle@fct.unl.pt
[c] Dr. N. M. M. Moura, Dr. C. NfflÇez, Prof. J. L. Capelo, Prof. C. Lodeiro
ProteoMass Scientific Society, Madan Parque, Rua dos Inventores
2825-182, Caparica (Portugal)
[d] Dr. C. NfflÇez
Department of Geographical and Life Sciences
Canterbury Christ Church University, CT1 1QU Canterbury (UK)
[e] Dr. S. M. Santos, Dr. F. A. Almeida Paz
Concerning our studies on structural modification of meso-
tetraarylporphyrins at their b-pyrrolic positions, namely
through a formyl group,[19] we report here an efficient and
facile access to a new 3,5-di-substituted pyridine bearing two
Department of Chemistry and CICECO
University of Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402270.
Chem. Eur. J. 2014, 20, 6684 – 6692
6684
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
1
porphyrin-2-ylmethyl moieties (2) from 2-formyl-5,10,15,20-
tetraphenylporphyrin (1). Based on the ability of porphyrins to
be used as fluorescent and colorimetric chemosensors and
also on our research interest on this topic[20–25] we envisaged
that the presence of the two porphyrinic units linked by the
pyridine could potentiate the ability of the new system to rec-
ognize and to bind different metal ions.
The H NMR spectrum of this highly symmetric compound
shows, in the low field region, a singlet at d=8.26 ppm due to
the H-3 proton, one AB system at d=8.83 ppm and four doub-
lets at d=8.74, 8.66, 8.52, and 8.38 ppm, which correspond to
the remaining b-pyrrolic protons. The signals from the pyridine
moiety appear as two singlets at d=7.89 ppm (H-2’’ and H-6’’)
and d=6.58 ppm (H-4’’) separated from the resonances due
the meso-phenyl protons. In the aliphatic region the singlet at
d=4.10 ppm was attributed to the resonances of the ꢀCH2
protons; the resonance of the corresponding aliphatic carbon
appears in the 13C NMR spectrum as distinctive signal at d=
33.5 ppm. The proton and carbon assignments were per-
formed with the support of 2D NMR spectroscopic techniques,
namely COSY, HSQC, and HMBC (Figures S1–S5 in the Support-
ing Information). The MALDI mass spectrum with a peak at
m/z 1332.4 corresponding to the molecular ion [M+H]+ is also
compatible with the structure of 2. With this study it was dem-
onstrated that lanthanum(III) triflate plays an important role in
the synthesis of 2 contributing for a clean reaction and high
yield of the desired compound.
The sensing ability of the new derivative towards Zn2+
,
Cu2+, Hg2+, Cd2+, and Ag+ was carried out in solution, gas
phase, and by using solid-supported polymers. The preferential
stoichiometry and binding mode in solution was confirmed by
molecular dynamics simulations. In addition, the structure of
ZnII complex of 3,5-bis(5,10,15,20-tetraphenylporphyrin-2-ylme-
thyl)pyridine was unequivocally elucidated by single-crystal X-
ray diffraction.
Results and Discussion
During our studies on the structural modification of meso-tet-
raarylporphyrins through a b-formyl group, we found that the
simple reflux of 2-formyl-5,10,15,20-tetraphenylporphyrin 1 in
toluene in the presence of piperidine affords the new 3,5-bis-
porphyrinylpyridine 2 in 36% yield (Scheme 1, a). A literature
The photophysical characterization of compound 2 was per-
formed in chloroform solution at 298 K and the main photo-
physical data are reported in Table 1. The absorption, excita-
tion, and emission spectra of compound 2 as well as the emis-
sion spectra obtained from the solid state of the same deriva-
tive are shown in Figure 1.
The absorption spectrum shows the typical features of free
base porphyrins due to p–p* transitions with the highly in-
Table 1. Photophysical data of compound 2 in CHCl3 and in solid state at
298 K.
lmax [nm]
(loge [dm3 Mꢀ1 cmꢀ1])
lem
Stokes
shift [cm-1]
FFlu
lem solid
[nm]
[nm]
418 (5.56)
516 (4.49)
550 (4.01)
592 (3.96)
647 (3.70)
651, 719
2.5”106
0.03
662, 720, 822
Scheme 1. Synthetic route of 3,5-bisporphyrinylpyridine 2. Reagents and
conditions: a) toluene, heat at reflux, 19 h, 36 %; b) [La(OTf)3], toluene, heat
at reflux, 19 h, 54 %.
survey showed that a similar reactivity was reported by Poirier
and Burrows for simpler aldehydes like benzaldehyde and ana-
logues.[26–28] Based on the proposed mechanism (Scheme S1 in
the Supporting Information) namely electrophilic additions to
the formyl group and the formation of enamines involving pi-
peridine, and knowing the potentialities of [La(OTf)3] as
a Lewis acid even when water is present[29] we decided to
repeat the condensation in the presence of this reagent. Under
the new experimental conditions (Scheme 1, b) the desired
compound 2 was isolated, after workup and purification, in
a comfortable yield of 54%. The structure was unambiguously
established by spectroscopic data, namely NMR spectroscopy,
UV/Vis spectroscopy, and mass spectrometry techniques (see
NMR spectroscopic data in the Supporting Information).
Figure 1. Absorption (Abs) and normalized emission (Emiss) and excitation
(Exct) spectra of compound 2 in CHCl3 ([2]=1.00”10ꢀ6 m, lexc =592 nm and
lemiss =719 nm) and emission spectrum in the solid state at 298 K.
Chem. Eur. J. 2014, 20, 6684 – 6692
www.chemeurj.org
6685
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
tense Soret band or B band (due to the allowed transition
from S0!S2) at 418 nm and four weak Q bands (due to the
transition from S0!S1) between 516 and 647 nm. The perfect
match between the absorption and the excitation spectra rules
out the presence of any emissive impurity. The fluorescence
emission spectrum of compound 2 obtained after excitation at
592 nm presents two bands centered at 651 and 719 nm,
which are characteristic of porphyrin derivatives.
Compound 2 shows a Stokes shift of 2.5x106 cm-1, which is
indicative of a change in the electronic nature of the excited
state compared with that of the ground state. The fluores-
cence quantum yield (FFlu), determined by the internal refer-
ence method with respect to a solution of crystal violet in
methanol as a standard ([FFlu]=0.54),[30,31] is 0.03.
The emission spectrum of the solid powder of ligand 2 was
also measured by using a fiber optic system connected to the
Horiba JY Scientifc Fluoromax 4. The solid-state spectrum
shows fluorescence bands between 662–822 nm with maxi-
mum intensities different to the ones observed in solution.
The sensorial ability of ligand 2 towards the metal cations
was studied by adding aliquots of Zn2+, Cu2+, Hg2+, Cd2+, and
Ag+ in acetonitrile to a solution of 2 in CHCl3. These titrations
promoted significant changes in the ground and excited states
as can be seen in Figure 2 for the studies performed with Zn2+
and also in Figures S6 to S8 in the Supporting Information for
the other metals. After titration with all the aforementioned
metal ions, a red shift of the initial Soret band centered at
418 nm was observed in the absorption spectra that varied be-
tween 425 and 443 nm. In the Q-band region the final altera-
tions were dependent on the sensing metal. For Zn2+ and
Cu2+, only two Q bands centered at about 540 and 600 nm
were detected (Figure 2A). For Hg2+ and Cd2+ the decrease of
the Q band at 516 nm is accompanied by the appearance of
a new band at about 663 nm; these effects are probably due
to different interactions between the metal ions and the elec-
tron lone-pair of the inner N atoms of the porphyrin macro-
cycle.
Figure 2. A) Spectrophotometric, and B) spectrofluorimetric titrations of 2 in
chloroform as a function of added Zn2+ in acetonitrile at 298 K. The inset
graphs show the absorption at 418 and 425 nm (A) and the normalized fluo-
rescence intensity at 608, 652, and 716 nm (B) ([2]=1.00”10ꢀ6 m,
lexc =536 nm). Inset photographs a and b: solution of 2 in CHCl3 before and
after addition of Zn2+, respectively, under visible light; c and d: solution of 2
in CHCl3 before and after addition of Zn2+, respectively, after excited at
365 nm by a UV lamp.
Considering the excited state, a decrease in the two bands
centered at 652 and 716 nm, due to the free base porphyrin
emission Q (0–0) and Q (0–0)(0–1)[32] was observed after the
addition of the explored metal ions. However, with the addi-
tion of Zn2+, such a decrease is accompanied by the appear-
ance of a new band at 608 nm (Figure 2B). This new emission
band, which increases with the addition of Zn2+, can be as-
signed to a metal-to-ligand charge transfer and indicates the
generation of a new fluorophore arising from the metal–por-
phyrin association.
metric changes were not observed after the titration of molec-
ular probe 2 with Ag+.
Considering the stability constants values (Slogb=15.46–
18.89) presented in Table 2 and the limit of detection (LOD;
39–99 ppb) and limit of quantification (LOQ; 79–199 ppb)
values presented in Table 3, we can conclude that ligand 2 is
an efficient molecular probe for the detection of Zn2+, Cu2+
Hg2+, and Cd2+ metal ions; all data are in accordance with
,
The alterations observed in the absorption spectrum of com-
pound 2 upon titration with Zn2+ resulted in a color change
from yellowish-brown to green. These data, together with the
appearance of the blue-shifted emission band that leads to
a remarkable color change in the emission from red to intense
orange (Figure 2), can be analytically explored to develop
a new type of Zn2+ chromogenic and fluorogenic molecular
device, as it can be concluded from the comparative fluores-
cent response for Hg2+, Cd2+, Cu2+, and Ag+. Spectrophoto-
Table 2. Stability constants for chemosensor 2 in the presence of Zn2+
,
Cu2+, Hg2+, Cd2+, and Ag+ in CHCl3 for an interaction 3:1 (metal/ligand)
at 298 K.
Interaction (M/L)
Slogb (Abs)
Slogb (Emiss)
Zn2+ (3:1)
Cu2+ (3:1)
Hg2+ (3:1)
Cd2+ (3:1)
Ag+
15.46ꢁ1.21”10ꢀ3
17.28ꢁ1.34”10ꢀ3
18.28ꢁ6.52”10ꢀ3
17.28ꢁ1.34”10ꢀ3
–
15.57ꢁ1.64”10ꢀ2
16.74ꢁ1.17”10ꢀ2
18.89ꢁ1.13”10ꢀ2
16.74ꢁ1.17”10ꢀ2
–
Chem. Eur. J. 2014, 20, 6684 – 6692
www.chemeurj.org
6686
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
lanthanide complexes.[33–37] The fluorescence emission proper-
ties of the new hybrid inorganic–organic materials were stud-
ied using an optical fiber device connected to the spectro-
fluorimeter.
Table 3. Limits of detection (LOD) and quantification (LOQ) in ppm for
Zn2+, Cu2+, Hg2+, Cd2+, and Ag+ with compound 2.
Metal ion
LOD
LOQ
Zn2+
Cu2+
Hg2+
Cd2+
Ag+
0.039ꢁ0.001
0.039ꢁ0.001
0.099ꢁ0.001
0.068ꢁ0.001
–
0.079ꢁ0.001
0.079ꢁ0.001
0.199ꢁ0.001
0.137ꢁ0.001
–
The results obtained after spraying the film with an 1”
10ꢀ3 m aqueous solution containing Hg2+ or Zn2+ at room
temperature are shown in Figure 3. Drastic color changes were
observed with both metals. In addition, it was observed
quenching of the fluorescence emission of the film after spray-
ing with a solution of Zn2+, whereas an enhancement was ob-
served in the presence of Hg2+. The results obtained show
a clear interaction of these metal ions with chemosensor 2.
a 1:3 ligand-to-metal stoichiometry (see later theoretical stud-
ies).
To confirm the high recognition efficiency of the new
system, the titration of the non-substituted synthetic precursor
5,10,15,20-tetraphenylporphyrin (TPP) with Hg2+, Cu2+, Zn2+
,
Cd2+, and Ag+ (data not shown) was also performed. No sig-
nificant changes were detected in the absorption and emission
spectra when the same amount of the metal ion was added.
To observe some changes in the ground and excited states the
addition of a large amount of the metal ions (ꢂ10 equiv) to
TPP was required; the stability constants obtained for those in-
teractions are much lower than the ones found for compound
2 (ꢀlogꢂ6 vs. 17).
The sensing ability of 3,5-bisporphyrinylpyridine 2 in the gas
phase, towards Zn2+, Cu2+, Hg2+, Cd2+, and Ag+ ions was
studied by MALDI-TOF MS by using the “dried-droplet” ap-
proach and “layer-by-layer” deposition. In these studies, com-
pound 2 was dissolved in chloroform and the metal salts in
acetonitrile. The results of the MALDI-TOF MS metal ion titra-
tions of compound 2 with the different metals are summarized
in Table S1 (see the Supporting Information). In both methods
the porphyrin complex acts as an internal matrix.
As an example, the MALDI-TOF MS spectra obtained after
the titration of compound 2 with AgBF4, is shown in Figure S9
(see the Supporting Information). Before adding the metal salt,
the ion corresponding to the protonated ligand [2+H]+, m/z
1332.37 (100% relative abundance) is observed. After adding
1 equiv of Ag+, an ion with m/z 1438.06 (100% relative abun-
dance) corresponding to [2+Ag]+ is detected. After the addi-
tion of 2 and 3 equiv of Ag+, the ions, [2+2Ag]+· (m/z
1545.11) [2+3Ag]+ (m/z 1651.72) respectively, are also formed.
After the addition of 1 equiv of the respective metal ions, 1:1
metal-to-ligand species were also formed for Cu2+, Zn2+, and
Cd2+ with significant relative abundances, although with lower
m/z values (1 to 3 below the calculated values). In the same
conditions for Hg2+ the 1:1 species were also formed but with
low relative abundances. Peaks attributable to the formation
of 2:1 species were obtained for all the ions, with the excep-
tion of Hg2+, however 3:1 species were only detected for Cu2+
and Ag+ and, in the case of the later, they were formed with
low abundance. As it can be seen, this molecular probe was
able to detect all metals, including Ag+, in the gas phase.
Considering the possibility of using compound 2 as a dye in
a real sensors, low-cost polymers based on polymethylmethac-
rylate (PMMA) were prepared in the presence and in the ab-
sence of water, according to the strategy applied for emissive
Figure 3. Visual changes observed when PMMA film with chemosensor 2
was sprayed with an aqueous solution containing Hg2+ or Zn2+ at visible
light and after being excited at 365 nm using a UV lamp (top). Emission
spectra of the PMMA film doped with 2 and after spraying Zn2+ or Hg2+ at
room temperature (bottom).
Theoretical studies
The 3:1 binding mode of the Zn2+ cations to the 3,5-bispor-
phyrinylpyridine receptor 2, observed in solution, was as-
sessed, in its deprotonated form, by means of molecular dy-
namics simulations in explicit solvent, using classical molecular
mechanics force fields. This system was chosen as being repre-
sentative of the complexation modes of the receptor to the re-
maining metal cations. No restraints were applied to the in-
volved species, such that the nature of the interactions be-
tween the anions (receptor and BF4 ) and cations (Zn2+) were
ꢀ
entirely nonbonded (electrostatic and van der Waals). It should
be noted that the calculation of partial atomic RESP charges
for the receptor was performed using compound 3 (i.e., the re-
ceptor and two Zn2+ in the porphyrinic cores, as found in the
single-crystal X-ray structure), for which the total charge is
zero. This yielded a partial charge of +1.418 e for Zn2+ and
Chem. Eur. J. 2014, 20, 6684 – 6692
www.chemeurj.org
6687
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
ꢀ2.835 e for the receptor: the total charges correspond to
about 70% of the known formal charges of both species (+2 e
and ꢀ4 e, respectively), which ultimately result in scaled-down
electrostatic interactions between the cations and the receptor.
All Zn2+ cations were, thus, assigned a partial charge of
ꢀ
+1.418 e and those of BF4 (required for balancing the total
charge of the system) were scaled as to yield a total charge of
ꢀ0.709 e (see the Experimental Section for further details).
The lowest energy molecular-mechanics co-conformation of
ꢀ
24ꢀ·3Zn2+·2BF4 is shown in Figure 4. Two Zn2+ cations are lo-
Figure 5. Spatial distribution function of the 24ꢀ·3Zn2+·2BF4ꢀ complex. The
isosurfaces have been drawn at the 100% isolevel, meaning that they en-
compass the totality of the positions occupied by the involved species
during the entire course of the MD simulations. Isosurfaces pertaining to the
receptor, cations, and counteranions are in red, green, and teal, respectively.
scaled partial charges underestimate the electrostatic interac-
tions between charged species, which, in this case, underesti-
mate the highly favorable interactions between the cation and
ꢀ
the pyridine nitrogen and the cation and the BF4 counteran-
ions. It is, thus, likely that the interactions in the real case will
stabilize more this association than what is being inferred from
the simulation. Finally, the isosurfaces pertaining to the recep-
tor itself and the two remaining cations indicate that both cat-
ions are kept inside the porphyrinic core, as otherwise expect-
ed. It seems that the stability of the cation-to-pyridine associa-
tion can be assigned to the combined shielding effect of the
Figure 4. Lowest energy molecular mechanics co-conformation involving the
ꢀ
three Zn2+ cations, the 3,5-bisporphyrinylpyridine receptor and the two BF4
counteranions. Hydrogen atoms have been omitted for the sake of clarity.
Color code: green: Zn; blue: N; gray: C; teal: F; brown: B.
ꢀ
cated inside the porphyrinic cores, with N···Zn2+ distances
ranging from 1.90 to 1.97 Š, whereas the third cation binds to
the pyridine nitrogen, with N···Zn2+ distance of 1.93 Š, stabi-
two neighbor meso-phenyl rings and the BF4 counteranions,
along with the polarity of the solvent. A more polar solvent
such as ethanol or acetone would probably easily disrupt the
whole ensemble, since the solvent molecules would easily sta-
bilize the ionic species. This has, however, not been studied.
ꢀ
lized by the two BF4 counteranions. The porphyrin rings are
parallel-displaced relatively to each other, such that one of the
phenyl units from each porphyrin is placed above the cation
inside the neighboring porphyrin, eventually stabilizing the
cation through p···Zn2+ electrostatic interactions.
X-ray diffraction
The results from five independent 20 ns long simulations, in
explicit CHCl3, reveal that the binding arrangement in Figure 4
is stable in solution. The spatial distribution functions of the
solutes (receptor, cations, and counteranions) during the total
100 ns long simulation (all structures were fitted to a reference
structure using the C and N atoms of pyridine) is shown in
Figure 5. The isosurfaces encompass the totality of the posi-
tions occupied by the component atoms throughout the simu-
lation. The Zn2+ cation above the pyridine shows little mobility
relatively to the nitrogen atom of the pyridine, indicating that
the N···Zn2+ interaction is conserved, whereas the isosurface
The Zn2+ complex 3 was successfully crystallized from a mix-
ture of CH2Cl2/hexane, which allowed the isolation of crystals
whose structure was fully elucidated using single-crystal X-ray
diffraction at 150 K (see the technical details given in the Sup-
porting Information).[38,39] The crystal structure could be de-
scribed either in the non-centrosymmetric Cc space group or
in the centrosymmetric C2/c one. The compound contains,
nevertheless, a remarkable 3,5-bisporphyrinylpyridine molecu-
lar unit composed of two 5,10,15,20-tetraphenylporphyrins
bridged together by a 3,5-disubstituted pyridine as depicted in
Figure 6 (see also Figure S11 in the Supporting Information for
the corresponding atomic labeling). We note that the ambigui-
ty related with the space group of this compound (see the
Supporting Information for additional details) is strongly relat-
ed with both the bulky nature of the 3,5-bisporphyrinylpyri-
dine unit (which prevents an effective close packing) and the
fact that the molecule is, indeed, centrosymmetric: a mirror
plane bisects the bridging 3,5-disubstituted pyridine and crys-
tallographically the two moieties could even be related by a C2
axis (hence the Cc versus C2/c dichotomy for the space
groups). Because the non-centrosymmetric structure describes
in a much better pictorial fashion the crystal structure, the
ꢀ
corresponding to the counteranions suggest that both BF4
anions and the cation persist as a loosely bounded, neutral,
ion-triplet. The shape of the isosurface of the counteranion in-
dicates that the cation is relatively shielded from the solvent
molecules by both counteranions, the pyridine and phenyl
units of the receptor. The meso-phenyl units from both por-
phyrins neighboring the pyridine bridge seem to be almost
parallel to the pyridine ring during most of the time, suggest-
ing little mobility of this ensemble (see the Supporting Infor-
mation for additional images), which can be associated with
high stability of the association. It should be noted that the
Chem. Eur. J. 2014, 20, 6684 – 6692
www.chemeurj.org
6688
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Figure 7. Fragment of the one-dimensional coordination polymer present in
compound 3, emphasizing the inter-3,5-bisporphyrinylpyridine connectivity
established between the nitrogen atom of the interporphyrin bridging 3,5-
disubstituted pyridine and a Zn2 cation from a neighboring 3,5-bisporphyri-
nylpyridine unit. The length of this connection varies slightly according to
the space group in which the structure was refined, being the longest
2.225(19) Š for the centrosymmetric model (in C2/c).
Figure 6. Perspective views of the 3,5-bisporphyrinylpyridine molecular unit
composing the crystal structure of compound 3. The interporphyrin bridge
ensured by the 3,5-disubstituted pyridine is highlighted with the bonds de-
picted in orange. For additional drawings depicting the atomic labeling and
crystal packing features see Figures S11 to S13 in the Supporting Informa-
tion.
ular contacts). Consequently, the crystal packing is mostly
mediated by the need to effectively fill the available space
leaving, nevertheless, large voids in the structure (Figure S13 in
the Supporting Information), which are filled with highly disor-
dered solvent molecules (could not be located in the per-
formed crystallographic studies).
structural discussion in the following paragraphs will be fo-
cused on this structural determination being, nevertheless,
valid for both space groups.
In the Cc space group (3_Cc), and as expected from the
chemical synthesis, the structure contains two crystallographi-
cally independent Zn2+ metallic centers: Zn1 is tetracoordinat-
ed to four pyrrole rings of the porphyrin molecule with an
overall geometry resembling a distorted square, {ZnN4}; Zn2 is
instead five-coordinated exhibiting a typical distorted square-
pyramidal coordination environment, {ZnN5}, in which the
apical position is composed of a ZnꢀN bond with the bridging
3,5-disubstituted pyridine of a neighboring dimer. Noteworthy,
for 3_Cc the ZnꢀN bonds fall within a relatively narrow range
(1.943(11)–2.19(2) Š; see Figure S11 and Table S2 in the Sup-
porting Information for detailed tabulated data), with the
longer interaction corresponding to the aforementioned inter-
dimer bridge (for the C2/c centrosymmetric model this bond is
even slightly longer as depicted in Figure 2: 2.225(19) Š).
The inter-3,5-bisporphyrinylpyridine ZnꢀN coordinative
bonds are at the origin of an undulated one-dimensional (1D)
coordination polymer in which the 3,5-bisporphyrinylpyridine
units are distributed in a zigzag herringbone fashion as shown
in Figure 7 (see also Figure S12 in the Supporting Information).
The coordination polymer is, in this way, highly distorted
which prevents the existence of structurally significant supra-
molecular contacts in the crystal structure of compound 3
(Table S3, in Supporting Information, tabulates the supramolec-
The obtained results show that 3,5-bisporphyrinylpyridine 2
is a useful potential probe for metal ion detection. Species
with different metal-to-ligand ratios were formed not only in
the gas phase, but also in solution and in the solid state.
The main driving force for the formation of the 3:1 complex
in solution may reside in entropic considerations. Although the
3:1 binding mode is favored in solution, as was found through
both experiment and MD simulations, this certainly is not what
happens in the solid state. In solution, the average volume oc-
cupied by the complex (receptor+cations+counteranions) is
smaller than the sum of the individual component volumes, in
which case the volume variation during complexation leads to
a greater volume available for the solvent molecules.
Since a positive volume variation can be correlated with an
increase in the entropy variation (i.e., greater DS), the cation-
to-receptor association free energy is enhanced (i.e., made
more negative) as the entropic contribution is deducted from
the enthalpy (DG=DHꢀTDS). However, as the solvent-to-
solute ratio decreases, during crystallization, the greater
volume variation is achieved by association of distinct recep-
tors, mediated through the pyridine nitrogen and a core
cation, eventually leading to 2:1 binding mode of the X-ray
Chem. Eur. J. 2014, 20, 6684 – 6692
www.chemeurj.org
6689
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Analytical TLC was carried out on precoated sheets with silica gel
(Merck 60, 0.2 mm thick).
structure. This hypothesis has not been addressed, mainly be-
cause of the methodological difficulty in calculating the en-
tropic contributions to the association free energy.
Chemicals and starting reagents
The above considerations can explain the observed differen-
ces of stoichiometry and structure in the condensed phases.
The observation of several stoichiometries in the gas phase
can also be rationalized if we bear in mind that, although not
observed in the present case, the ions formed when MALDI is
used may include adducts with the matrix, counterions, and
the solvent. In the present case no matrix was used, and the
removal of several monolayers by laser ablation may lead to
the formation of aggregates of neutral species, protonated
and deprotonated ligands and other charged particles. The for-
mation of the observed species is, very likely, dependent on
the the different counterions and different oxidation states
and ionic radii of the metal centers and probably occurs
through complex aggregation/dissociation processes (involving
acid/base and redox reactions) in the hot plume.
[Cu(BF4)2]·6H2O,
[Zn(BF4)2]·xH2O,
[Cd(CF3SO3)2]·xH2O,
[Hg-
(CF3SO3)2]·xH2O, and [AgBF4] xH2O were purchased from Strem
Chemicals, Sigma–Aldrich, or Solchemar. All these chemicals were
used without further purification. The solvents were obtained from
Panreac and Riedel-de-Häen and were used as received or distilled
and dried using standard procedures according to the literature
procedures.[40]
Gas-phase measurements
The MALDI-MS analyses were performed in a MALDI-TOF-TOF MS
model Ultraflex II (Bruker, Germany) equipped with nitrogen (BIO-
SCOPE group). Each spectrum represents accumulations of 5”
50 laser shots. The reflection mode was used. The ion source and
flight tube pressure were less than 1.80”10ꢀ7 and 5.60”10ꢀ8 Torr,
respectively. The MALDI mass spectra of the soluble samples (1 or
2 mgmLꢀ1) were recorded by using the “dried droplet” and the
“layer-by-layer” sample preparation methods. In both methods the
ligands were dissolved in chloroform and the metal salts in aceto-
nitrile but the introduction in the sample holder was different. In
the “dried-droplet” method, the two solutions containing the
ligand (1 mL) and the metal salt (1 mL) were mixed and then ap-
plied in the MALDI-TOF MS sample holder. In the “layer-by-layer”
method, a solution of each ligand was spotted in the MALDI-TOF
plate and then dried; subsequently, 1 mL of the solution containing
the metal salt was placed on the sample holder, which was then
inserted in the ion source. In this case, the chemical reaction be-
tween the ligand and the metal salts occurred in the holder, and
the complex species were produced in gas phase.
Conclusion
We have obtained and fully characterized a new 3,5-bispor-
phyrinylpyridine 2 through an efficient synthetic approach cat-
alyzed by lanthanum triflate. The unexpected increase in the
emission intensity of molecular probe 2 in the presence of
Zn2+ is a very important and promising result. The ligand titra-
tion experiments with this metal cation indicate a 1:3 ligand-
to-metal complex stoichiometry with a high association con-
stant (Kass ꢂ15.50). The preferential stoichiometry and binding
modes of 2 to Zn2+ were confirmed through theoretical calcu-
lations. Additionally, the results obtained by MALDI-TOF MS
Spectrophotometric and spectrofluorimetric measurements
confirm the gas phase sensing abilities of 2 towards Zn2+
,
Cu2+, Hg2+, Cd2+, and Ag+. The crystal structure of the Zn2+
complex 3 was fully and unequivocally elucidated by using
single-crystal X-ray diffraction.
Absorption spectra were recorded on a JASCO V-650 spectropho-
tometer and fluorescence emission spectra were recorded on
a Horiba Jobin–Yvon Fluoromax 4 spectrofluorimeter from the BIO-
SCOPE group. The linearity of the fluorescence emission versus the
The results obtained after doping PMMA films with chemo-
sensor 2 clearly show a promising system for the detection of
Hg2+ and Zn2+ in aqueous solution, enabling 2 to discriminate
between the two metal ions.
concentration was checked in the concentration range used (10ꢀ4
–
10ꢀ6 m). The correction of the absorbed light was performed when
it was considered necessary. The spectrophotometric characteriza-
tions and titrations were performed by preparing a stock solution
of the compound in chloroform (ca., 10ꢀ3 m) in a 10 mL volumetric
flask. The studied solutions were prepared by appropriate dilution
of the stock solution up to 10ꢀ5–10ꢀ6 m. Titrations of molecular
probe 2 were carried out by the addition of microliter amounts of
standard solutions of the metal ions (Zn2+, Cu2+, Hg2+, Cd2+, and
Ag+) in acetonitrile. All the measurements were performed at
298 K.
Experimental Section
General remarks
1H and 13C solution NMR spectra were recorded on Bruker Avance
500 (500.13 and 125.76 MHz, respectively) spectrometer. CDCl3 was
used as solvent and tetramethylsilane (TMS) as internal reference;
the chemical shifts are expressed in d (ppm) and the coupling con-
stants (J) in Hertz (Hz).
Unequivocal 1H assignments were made using 2D COSY (1H/1H),
whereas 13C assignments were made on the basis of 2D HSQC
(1H/13C) and HMBC (delay for long-range J C/H couplings were opti-
mized for 7 Hz) experiments. Mass spectra were recorded using
MALDI TOF/TOF 4800 Analyzer, Applied Biosystems MDS Sciex,
with CHCl3 as solvent and without matrix. Mass spectra HRMS were
recorded on APEXQe FT-ICR (BrukerDaltonics, Billerica, MA) mass
spectrometer using CHCl3 as solvent; in m/z (rel.%). Column chro-
matography was carried out using silica gel (Merck, 35–70 mesh).
Luminescence quantum yields of compound 2 were measured
using a solution of crystal violet in methanol as standard ([F]=
0.54),[30,31] and all values were corrected taking in account the sol-
vent refractions index.
The stability constants for the interaction of ligand 2 with Zn2+
,
Cu2+, Hg2+, Cd2+, and Ag+ were calculated by using HypSpec soft-
ware.[41]
Fluorescence spectra of solid samples were recorded using a fiber
optic system connected to a Horiba Jobin–Yvon Fluoromax 4 spec-
trofluorimetric exciting the solid compound 2 at l=592 nm. The
limit of detection (LOD) and the limit of quantification (LOQ) for
metal ions were performed having in mind their use for real anion
Chem. Eur. J. 2014, 20, 6684 – 6692
www.chemeurj.org
6690
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
detection and for analytical applications. For these measurements,
ten different analyses for the selected receptor were performed in
order to obtain the LOQ. The LOD was obtained by the formula:
inic cores, for which the total charge is zero), at the HF/6–31G*//
B3LYP/6–31G* level using Gaussian 09, revision A.02.[50] This proce-
dure yielded a partial charge of +1.418 e for Zn2+ and ꢀ2.835 e
for ꢀthe receptor. To obtain a neutral system, the partial charges of
BF4 were scaled as to yield a total charge of ꢀ0.709 e (2qBF4
+
ydl ¼ yblank þ 3 std
3
q
rec +3qZn =0.0 e). Simulation boxes (ca., 64.5”64.5”64.5 Š after
equilibration) were constructed from one receptor, three cations
and two counteranions inside a cubic box containing 2058 chloro-
form molecules. Simulations began with an initial solvent minimi-
zation procedure for the removal of close contacts between solute
and solvent molecules, with the solute placed under strong posi-
tional restraints. The restraints were then removed, and the whole
system was allowed to relax. Subsequently, a weak positional re-
straint was applied to the solute, and the system was heated to
300 K in the NVT ensemble for 0.5 ns, using the “velocity rescaling
with stochastic term” thermostat (tcoupling =2.0 ps), and equilibrated
under the NPT ensemble during 2 ns using the Berendsen barostat
(tcoupling =5.0 ps) until the density of the system was brought to
a plateau. The positional restraints used throughout both heating
and equilibration procedures were definitely removed during the
data collection period (5 independent 20 ns in the NPT ensemble).
The LINCS algorithm was used to constrain all hydrogen involving
bond distances at their equilibrium values; periodic boundary con-
ditions, along with a 10 Š nonbonded cutoff were used; long-
range electrostatic interactions were calculated with the particle
mesh Ewald (PME) method; snapshots were collected every 0.2 ps.
Prior to the calculation of the spatial distribution functions, all tra-
jectories were concatenated and fitted to the first structure in the
trajectory using the pyridine heavy atoms (C,N). The isosurfaces
were drawn at the 100% isolevel, meaning that they encompass
the totality of the positions occupied by the solute atoms during
the course of the simulations.
in which ydl is the signal detection limit and std is the standard
deviation.
Preparation of PMMA polymer films doped with compound
2
The preparation of the PMMA films was performed by dissolving
the PMMA powder (0.1 g) in chloroform, followed by addition of
compound 2 (0.001–0.005 g) dissolved in the same solvent. The
polymer films were obtained after solvent evaporation at 408C
under vacuum for 24 h.[42,43] Due to the spectroscopic characteris-
tics the films doped with 0.005 g of the ligand 2 were selected for
the studies with the metal ions.
Synthesis of the organic ligand
Synthesis of the precursor porphyrin: The 2-formyl-5,10,15,20-
tetraphenylporphyrin 1 was prepared from 5,10,15,20-tetraphenyl-
porphyrinatocopper(II), N,N’-dimethylformamide (DMF) and phos-
phorus oxychloride (POCl3), according to literature procedure.[44]
Synthesis
of
3,5-bis(5,10,15,20-tetraphenylporphyrin-2-yl-
methyl)pyridine: [La(OTf)3] (20 mol%, 4.6 mmol, 2.7 mg) and piperi-
dine (1.5 equiv, 35.0 mmol, 3.6 mL) were added to a solution of 2-
formyl-5,10,15,20-tetraphenylporphyrin (23.0 mmol, 15.0 mg) in dry
toluene (2.0 mL), which was then heated at reflux for 19 h. After
cooling, the reaction mixture was washed with water and extracted
with chloroform. The organic phase was dried (Na2SO4) and the sol-
vent was evaporated under reduced pressure. The crude mixture
was submitted to column chromatography (silica gel) using tolu-
ene as eluent. The compound 2 was isolated in 54% yield and full
characterized by NMR spectroscopy, mass spectrometry and UV/Vis
techniques.
Crystallization of the Zn2+ derivative of 3,5-bis(5,10,15,20-
tetraphenylporphyrin-2-ylmethyl)pyridine 3
Compound 2 was dissolved in a minimal amount of CH2Cl2 in
a vial. A few drops of [Zn(BF4)2]·xH2O in CH3CN were added to this
solution and a change in the mixture color from brown to green
was observed in accordance with the formation of complex 3. The
vial was filled with hexane and sealed. From the crystallization pro-
cess was obtained the crystal of the Zn2+ derivative of 3,5-
bis(5,10,15,20-tetraphenylporphyrin-2-ylmethyl)pyridine (3), which
was fully elucidated by using single-crystal X-ray diffraction.
3,5-Bis(5,10,15,20-tetraphenylporphyrin-2-ylmethyl)pyridine (2):
1H NMR (500 MHz, CDCl3): d=8.83 (4H, AB, J=4.8 Hz, H-b), 8.74
(2H, d, J=4.8 Hz, H-b), 8.66 (2H, d, J=4.8 Hz, H-b), 8.52 (2H, d, J=
4.8 Hz, H-b), 8.38 (2H, d, J=4.8 Hz, H-b), 8.26 (2H, s, H-3), 8.26–8.15
(8H, m, H-o-Ph), 7.89 (2H, s, H-2’’ and H-6’’), 7.76–7.61 (20H, m, H-
o,m,p-Ph), 7.45 (2H t, J=7.6 Hz, H-m,p-Ph), 7.35 (2H t, J=7.6 Hz, H-
m,p-Ph), 7.27 (4H, t, J=7.7 Hz, H-m,p-Ph), 7.10 (4H, t, J=7.7 Hz, Ar-
H-m, p-Ph), 6.58 (1H, s, H-4’’), 4.10 (4H, s, H-1’), ꢀ2.79 ppm (4H, s,
N-H);13C NMR (125 MHz, CDCl3): d=147.5 (C-2’’), 142.2, 142.1, 141.8,
141.4, 135.9 (C-4’’), 135.8, 134.6, 134.5, 134.1, 133.3, 131.9, 130.6,
129.0, 128.2, 128.0, 127.7, 127.3, 126.8, 126.65, 126.61, 126.2, 120.5,
120.1, 119.6, 119.0, 33.5 ppm (C-1’); UV/Vis (CHCl3): lmax (loge)=
418.0 (5.56), 516.0 (4.49), 550.0 (4.01), 592.0 (3.96), 647.0 nm
(3.70 dm3 mꢀ1 cmꢀ1); MS (MALDI): 1332.4 [M+H]+; HRMS-ESI: m/z
calcd (%) for C95H66N9: 1332.5441 [M+H]+; found: 1332.5395.
Acknowledgements
Authors are grateful to the Universidade de Aveiro, Fundażo
para a CiÞncia e a Tecnologia (FCT), European Union, QREN,
FEDER and COMPETE for funding the QOPNA research unit
(project
PEst-C/QUI/UI0062/2013,
FCOMP-01-0124-FEDER-
037296). We acknowledge the Portuguese National NMR Net-
work (RNRMN), supported by funds from FCT, Scientific PRO-
TEOMASS Association (Portugal), CICECO (PEst-C/CTM/LA0011/
2013, FCOMP-01-0124-FEDER-037271) and REQUIMTE (PEst-C/
EQB/La0006/2013) for general funding and Fundażo para
a CiÞncia e a Tecnologia (FCT) for specific funding towards the
purchase of the single-crystal X-ray diffractometer. N.M.M.M.
and S.M.S. thank FCT/MEC for their Postdoctoral grant SFRH/
BPD/84216/2012 and SFRH/BPD/64752/2009. C.N. thanks the
Xunta de Galicia (Spain) for her postdoctoral contract (I2C pro-
Theoretical studies
Atomic parameters for the 3,5-bisporphyrinylpyridine receptor and
the zinc cation were taken from the GAFF force field[45] using Ante-
chamber,[46] whereas chloroform was described with parameters
taken from Fox et al.[47] Parameters for the BF4 anions were those
ꢀ
described by Wenchuan Wang and co-workers.[48] Calculation of
atomic RESP[49] fitted partial charges for the receptor were calculat-
ed on compound 3 (i.e., the receptor and two Zn2+ in the porphyr-
Chem. Eur. J. 2014, 20, 6684 – 6692
www.chemeurj.org
6691
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
[33] M. D. McGehee, T. Bergstedt, C. Zhang, A. P. Saab, M. B. O’Regan, G. C.
Bazan, V. I. Srdanov, A. J. Heeger, Adv. Mater. 1999, 11, 1349–1354.
[34] J. Kai, D. F. Parrab, H. F. Brito, J. Mater. Chem. 2008, 18, 4549–4554.
[35] A. Balamurugan, M. L. P. Reddy, M. Jayakannan, J. Phys. Chem. B 2009,
113, 14128–14138.
gram). We thank M. GraÅa O. Santana-Marques for the helpful
comments and discussion on MALDI-TOF MS studies.
Keywords: fluorescent probes · porphyrinoids · sensors · X-ray
diffraction · zinc
[36] J. C. Boyer, N. J. J. Johnson, F. C. J. M. van Veggel, Chem. Mater. 2009, 21,
2010–2012.
[37] H. Zhang, H. Song, B. Dong, L. Han, G. Pan, X. Bai, L. Fan, S. Lu, H. Zhao,
F. Wang, J. Phys. Chem. C 2008, 112, 9155–9162.
[38] See also the Supporting Information: experimental details on the
[1] K. M. Kadish, K. M. Smith, R. Guilard, in Handbook of Porphyrin Science,
Vols. 10–12, World Scientific Publishing Company, Singapore, 2010.
[2] Y.-Q. Weng, F. Yue, Y.-R. Zhong, B.-H. Ye, Inorg. Chem. 2007, 46, 7749–
7755.
[3] C.-Y. Li, X.-B. Zhang, Y.-Y. Dong, Q.-J. Ma, Z.-X. Han, Y. Zhao, G.-L. Shen,
R.-Q. Yu, Anal. Chim. Acta 2008, 616, 214–221.
[4] N. Kaur, S. Kumar, Tetrahedron 2011, 67, 9233–9264.
[5] J. S. Kim, D. T. Quang, Chem. Rev. 2007, 107, 3780–3799.
[6] L.-J. Fan, Y. Zhang, C. B. Murphy, S. E. Angell, M. F. L. Parker, B. R. Flynn,
W. E. Jones, Jr., Coord. Chem. Rev. 2009, 253, 410–422.
[7] L. N. Neupane, J.-Y. Park, J. H. Park, K.-H. Lee, Org. Lett. 2013, 15, 254–
257.
single-crystal X-ray diffraction studies performed for compound
3
(structural description in the non-centrosymmetric Cc and the centro-
symmetric C2/c space groups); additional structural drawings of the
crystal structure of the non-centrosymmetric model for 3 emphasizing
the arrangement of individual units to form the one-dimensional poly-
mer; tabulated geometrical data for the two crystallographically inde-
pendent Zn2+ centers and supramolecular contacts present in the non-
centrosymmetric model.
[39] Crystal data for 3_Cc (SQUEEZE data): C95H61N9Zn2, Mr =1459.27, mono-
clinic, space group Cc, Z=4, a=29.978(4), b=18.696(3), c=18.525(3) Š,
V=9205(2) Š3,
m(MoKa)=0.566 mmꢀ1
,
1cald =
[8] P. Roy, K. Dhara, M. Manassero, J. Ratha, P. Banerjee, Inorg. Chem. 2007,
46, 6405–6412.
b=117.550(6)8,
1.053 gcmꢀ3
.
Collected reflections 30936; independent reflections
14387 (Rint =0.1127). Crystal size 0.18”0.10”0.05 mm3. Final R1=
0.0973 [I>2s(I)] and wR2=0.2143 (all data). Data completeness to q=
25.358, 98.8%. Crystal data for 3_C2/c (SQUEEZE data): C95H61N9Zn2,
Mr =1459.27, monoclinic, space group C2/c, Z=4. Collected reflections
30935; independent reflections 8337 (Rint =0.1313). Final R1=0.0997
[I>2s(I)] and wR2=0.2545 (all data). Data completeness to q=25.358,
98.8%. CCDC-941872 (3_Cc) and CCDC-941873 (3_C2/c) contain the
supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
[9] G. Crivat, K. Kikuchi, T. Nagano, T. Priel, M. Hershfinkel, I. Sekler, N. Rose-
nzweig, Z. Rosenzweig, Anal. Chem. 2006, 78, 5799–5804.
[10] A. Xu, K.-H. Baek, H. N. Kim, J. Cui, X. Qian, D. R. Spring, I. Shin, J. Yoon,
J. Am. Chem. Soc. 2010, 132, 601–610.
[11] Z. Xu, J. Yoon, R. Spring, Chem. Soc. Rev. 2010, 39, 1996–2006.
[12] Y. Yang, J. Jiang, G. Shen, R. Yu, Anal. Chim. Acta 2009, 636, 83–88.
[13] D. W. Boening, Chemosphere 2000, 40, 1335–1351.
[14] M. V. B. Krishna, M. Ranjit, D. Karunasagar, J. Arunachalam, Talanta 2005,
67, 70–80.
[15] T. W. Clarkson, L. Magos, G. J. Myers, N. Engl. J. Med. 2003, 349, 1731–
1737.
[16] P. Grandjean, P. Weihe, R. F. White, F. Debes, Environ. Res. 1998, 77, 165–
172.
[17] a) H. N. Kim, W. X. Ren, J. S. Kim, J. Yoon, Chem. Soc. Rev. 2012, 41,
3210–3244; b) H.-Y. Luo, X.-B. Zhang, J.-H. Jiang, C.-Y. Li, J. Peng, G.-L.
Shen, R.-Q. Yu, Anal. Sci. 2007, 23, 551–555.
[18] N. M. M. Moura, C. NuÇez, S. M. Santos, M. A. F. Faustino, J. A. S. Cava-
leiro, M. G. P. M. S. Neves, J. L. Capelo, C. Lodeiro, ChemPlusChem 2013,
78, 1230–1243.
[19] J. A. S. Cavaleiro, A. C. TomØ, M. G. P. M. S. Neves, in Handbook of Porphy-
rin Science, Vol. 2 (Eds.: K. M. Kadish, K. M. Smith, R. Guilard), World Sci-
entific Publishing Company, Singapore, 2010, pp. 193–294.
[20] C. Lodeiro, F. Pina, Coord. Chem. Rev. 2009, 253, 1353–1383.
[21] C. Lodeiro, J. L. Capelo, J. C. Mejuto, E. Oliveira, H. M. Santos, B. Pedras,
C. NuÇez, Chem. Soc. Rev. 2010, 39, 2948–2976.
[40] W. L. F. Armarego, D. D. Perrin, in Purification of Laboratory Chemicals,
4th ed., Butterworth-Heinemann, Oxford, 1996.
[41] P. Gans, A. Sabatini, A. Vacca, Talanta 1996, 43, 1739–1753.
[42] D. B. A. Raj, B. Francis, M. L. P. Reddy, R. R. Butorac, V. M. Lynch, A. H.
Cowley, Inorg. Chem. 2010, 49, 9055–9063.
[43] O. Moudam, B. C. Rowan, M. Alamiry, P. Richardson, B. S. Richards, A. C.
Jones, N. Robertson, Chem. Commun. 2009, 6649–6651.
[44] N. M. M. Moura, M. A. F. Faustino, M. G. P. M. S. Neves, A. C. Duarte,
J. A. S. Cavaleiro, J. Porphyrins Phthalocyanines 2012, 16, 652–658.
[45] J. M. Wang, R. M. Wolf, J. W. Caldwell, P. A. Kollman, D. A. Case, J.
Comput. Chem. 2004, 25, 1157–1174.
[46] J. M. Wang, W. Wang, P. A. Kollman, D. A. Case, J. Mol. Graphics Modell.
2006, 25, 247–260.
[47] T. Fox, P. A. Kollman, J. Phys. Chem. B 1998, 102, 8070–8079.
[48] a) C. I. Bayly, P. Cieplak, W. D. Cornell, P. A. Kollman, J. Phys. Chem. 1993,
97, 10269–10280; b) W. D. Cornell, P. Cieplak, C. I. Bayly, P. A. Kollman, J.
Am. Chem. Soc. 1993, 115, 9620–9631.
[22] C. NuÇez, R. Bastida, A. Macías, L. Valencia, J. Ribas, J. L. Capelo, C. Lode-
iro, Dalton Trans. 2010, 39, 7673–7683.
[23] C. I. M. Santos, E. Oliveira, J. F. B. Barata, M. A. F. Faustino, J. A. S. Cava-
leiro, M. G. P. M. S. Neves, C. Lodeiro, J. Mater. Chem. 2012, 22, 13811–
13819.
[24] 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 2014, 70, 3361–3370.
[25] C. NfflÇez, M. Diniz, A. A. Dos Santos, J. L. Capelo, C. Lodeiro, Dyes Pigm.
2014, 101, 156–163.
[26] R. H. Poirier, R. D. Morin, M. McKim, E. Bearse, J. Org. Chem. 1961, 26,
4275–4278.
[49] X. Wu, Z. Liu, S. Huang, W. Wang, Phys. Chem. Chem. Phys. 2005, 7,
2771–2779.
[50] Gaussian 09, Revision A.02, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E.
Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Men-
nucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian,
A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara,
K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O.
Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro,
M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Ko-
bayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyen-
gar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B.
Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann,
O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin,
K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg,
S. Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cio-
slowski, D. J. Fox, Gaussian Inc., Wallingford CT, 2009.
[27] E. P. Burrows, R. F. Hutton, W. D. Burrows, J. Org. Chem. 1962, 27, 316–
317.
[28] W. D. Burrows, E. P. Burrows, J. Org. Chem. 1963, 28, 1180–1182.
[29] C. Alonso, V. I. V. Serra, M. G. P. M. S. Neves, A. C. TomØ, A. M. S. Silva,
F. A. A. Paz, J. A. S. Cavaleiro, Org. Lett. 2007, 9, 2305–2308.
[30] I. B. Berlman, in Handbook of Fluorescence Spectra of Aromatic Molecules,
2nd ed., Academic Press, New York, 1971.
[31] M. Montalti, A. Credi, L. Prodi, M. T. Gandolfi, in Handbook of Photo-
chemistry, 3rd ed., Taylor & Francis, Boca Raton, 2006.
[32] Z.-X. Han, H.-Y. Luo, X.-B. Zhang, R.-M. Kong, G.-L. Shen, R.-Q. Yu, Spec-
trochim. Acta Part A 2009, 72, 1084–1088.
Received: February 20, 2014
Published online on April 29, 2014
Chem. Eur. J. 2014, 20, 6684 – 6692
www.chemeurj.org
6692
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim