Pseudo-Crown Ethers as Novel Scaffolds for the Development of Al3+-Selective Fluorescent Probes

Article abstract of DOI:10.1002/ejoc.201900315

Herein, we report the systematic evaluation of the BODIPY series functionalized with pseudo-crown ethers against metal cations and assessment of their potential as novel off-on fluorescent probes selective for aluminum(III) cations.

Full text of DOI:10.1002/ejoc.201900315

A Journal of
Accepted Article
Title: Pseudo-crown ethers as а novel scaffold for the development of
Al3+-selective fluorescent probes
Authors: Mikhail A. Kozlov, Denis Y. Uvarov, Sergey A. Gorbatov,
Natalya G. Kolotirkina, Alexey D. Averin, Vadim V. Kachala,
Konstantin A. Lyssenko, Igor V. Zavarzin, and Yulia Volkova
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900315
Link to VoR: http://dx.doi.org/10.1002/ejoc.201900315
Supported by

10.1002/ejoc.201900315
European Journal of Organic Chemistry
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Pseudo-crown ethers as а novel scaffold for the development of
Al3+-selective fluorescent probes
Mikhail A. Kozlov,[a] Denis Y. Uvarov,[a,b] Sergey A. Gorbatov,[a] Natalya G. Kolotirkina,[a] Alexey D.
Averin,[c] Vadim V. Kachala,[a] Konstantin A. Lyssenko,[d] Igor V. Zavarzin,[a] and Yulia A. Volkova*[a]
Abstract: Herein, we report the systematic evaluation of the Bodipy
series functionalized with pseudo-crown ethers against metal cations
and assessment of their potential as novel off-on fluorescent probes
selective for aluminum(III) cations.
Introduction
Figure 1. Pseudo-crowns as selective chelating groups.
Aluminum is one of the most abundant elements in Earth's
crust representing approximately 8% of the total mineral content.
The trivalent aluminum cation is a serious environmental
studies dealing with compounds bearing simple flexible chelating
toxicant hazardous to plants and animals.1 It is not essential for
moieties,
such
as
tertiary
alkyl
amines,17
humans,2 but it can interact with proteins, enzymes, and
coenzymes and displace biologically essential metals, such as
magnesium, calcium, and iron.3 It was shown to bind to a
hydroxyethylenediamines,18 polyamines,19 and polythiols,20 as
highly efficient probes for the fluorescence detection of Al3+ ions.
Despite the impressive progress in this area, it is still a great
challenge to elaborate readily available fluorescent probes for
the selective and ratiometric detection of Al3+. Shortcomings of
many currently available probes are the non-equimolar complex
composition and enhanced emission intensity with no spectral
shift, as well as that their preparation requires difficult-to-obtain
starting materials.
number
hypoparathyroidism
of
secretory
and
granule
adynamic
proteins,
bone
causing
disease.4,5
Neurofibrillary degeneration and neuronal death associated with
Alzheimer's disease are believed to be induced by aluminum
accumulated in the brain.6 Therefore, the detection of Al3+ in the
presence of other alkali and alkaline earth metal ions is
particularly important for environmental protection and human
health.
Conventional methods used to analyze aluminum include
atomic absorption, inductively coupled plasma mass
spectroscopy, and inductively coupled plasma-atomic emission
spectrometry.7-9 Fluorescence methods have a number of
advantages over these techniques, such as high sensitivity,
noninvasiveness, and convenience.10 However, compared to
other metal cations, the detection of trivalent aluminum is a
challenging problem because of the lack of spectroscopic
characteristics, poor coordination ability, and strong hydration
ability. Molecular probes for fluorescence detection of aluminum
ions were extensively studied in the past decades.11 Rigid
imines,12 hydrazones,13 triazoles,14 a triazolyl-pyrrolidinyl linker,15
and crowns16 were revised as receptor groups for the design of
fluorescent probes for Al3+ as a hard acid. There are only a few
Recently, open-chain analogues of crown ethers, so-called
pseudo-crowns, have attracted much attention in fluorescence
sensing and bioimaging21 as easily accessible, highly promising
ligating agents for metals cations.22 Thus, Yoon et al. designed a
turn-on fluorescent probe for Cu2+ using N,N-bis(2-
acetoxyethyl)amine as the receptor group (Figure 1).23 Chang et
al. elaborated a Pb2+-selective fluorescent probe based on an
N,N-bis(2-ethoxycarbonylmethoxy)ethyl chelator, which is
efficient in water solutions and characterized by extremely low
detection limit.24 Inspired by these works, we decided to look for
pseudo-crown ether convenient for the development of turn-on
fluorescent probes selective for Al3+ ions. Recently, we found
that diverse boron dipyrromethenes (Bodipy) functionalized with
aza-crowns and their open-chain N,O-analogues exhibit rich
fluorescence properties promising for the detection of heavy
metal cations.25-27 Herein we report the synthesis and spectral
characterization of five novel Bodipy pseudo-crown-based
fluorescent Al3+ ion sensor molecules. We incorporated 2-((2-(2-
acetoxyethoxy)ethyl)amino)ethyl acetate pendant at the 3,5, and
8 positions of the Bodipy core using a phenyl linker to find the
optimal chemosensor structure for the ratiometric turn-on
detection of Al3+ ions based on UV-Vis and fluorescence
responses. Our particular interest was to investigate the
structure-chelating ability relationships for probes. The Bodipy
fluorophore was chosen because of its outstanding
photophysical properties such as a high absorption coefficient (ε
[a]
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of
Sciences, 47 Leninsky prosp., Moscow, 119991, Russian
Federation
E-mail:yavolkova@gmail.com
[b]
[c]
[d]
D. Mendeleev University of Chemical Technology of Russia,
Miusskaya sq. 9, 125047 Moscow, Russian Federation
Lomonosov Moscow State University, Department of Chemistry,
119991 Moscow, Russian Federation
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian
Academy of Sciences, Vavilov str. 28, GSP-1, Moscow, 119991,
Russian Federation
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201900315
European Journal of Organic Chemistry
FULL PAPER
> 50000 M-1 cm-1), a high fluorescence quantum yield, and high
photostability.28
phenyl, should minimize these interactions. The electronic
connection between the fluorophore and the chelator in the
probe is required for changes in both the color and emission.
The detection ability of a Bodipy-based probe can be tuned by
varying the nature of the chelating group and the binding mode
of the fluorophore, along with variations in the number of
receptor groups.
Results and Discussion
Design and synthesis
Hence, we synthesized probes 7-9, 11, and 12 (Figure 2).
The chemical structures of the sensor molecules investigated in
the present work and procedures for their synthesis are outlined
in Figure 2. The design of probes is based on the following
considerations. First, the ionic radius and the coordination
number of Al3+ are similar to those of Cu2+.29 A relatively small
change in the nature of the chelator can easily alter the probe
selectivity. The extension of pseudo-crown ether used in Yoon’s
chemosensor to Cu2+ provides a potential strategy for the
development of Al3+ selective probes (Figure 1). However, the
number of coordination centers in the novel chelator should not
exceed that in Chang’s probe, because the affinity for Pb2+ may
result in a decrease in the selectivity for Al3+. Second, the
fluorophore can affect the chelating ability of the flexible receptor
group due to intra- and intermolecular coordination and by
locking the free rotation of the chelator.30 The incorporation of a
receptor group into the fluorophore through rigid linkers, such as
Initially,
benzaldehyde
4
bearing
the
2-((2-(2-acetoxyethoxy)ethyl)amino)ethyl acetate group at the
para position was prepared as the key reagent for the
attachment of the chelator to the Bodipy fluorophore (Figure 2,
line a). Thus, diol 2 was synthesized in 73% yield by the reaction
of N-(2-hydroxyethyl)aniline with 2-(2-chloroethoxy)ethanol.24
Hydroxy groups in 2 were protected using acetic anhydride in
pyridine.31 The Vilsmeier reaction with electron-rich compound 3
and POCl3 – DMF afforded aldehyde 4 in 89% yield. The direct
synthesis of 8-substituted probes 7 and 8 was accomplished by
the condensation of aldehyde 430 with pyrroles 5, 6 in CH2Cl2 by
the stepwise treatment with trifluoroacetic acid (TFA), 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), triethylamine,
and boron trifluoride diethyl etherate (Figure 2, line b).
Figure 2. Syntheses of Bodipy-based probes.
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The removal of acetyl groups from compound 8 using LiOH
afforded probe 9 containing terminal OH groups in 78% yield.
The Knoevenagel condensation of aldehyde 4 with Bodipy 10
under Dean-Stark conditions gave 3-substituted probe 11 as the
major product (43% yield) and 3,5-disubstituted probe 12 as the
minor one (16% yield) (Figure 2, line c).
The structure of probe 8 was confirmed by single-crystal X-ray
diffraction (Figure 3). According to XRD, the geometry of 8 is
typical of this class of compounds. The plane of the meso-
phenyl ring is nearly orthogonal to the C3N2B mean plane (the
dihedral angle is 77.4°). Due to conjugation of the N(27) atom
with the phenyl ring (N(27), the bond lengths in the latter adopt a
slightly quinoid geometry, with the shortening of C(14)-C(15) and
C(17)-C(18) bonds down to 1383(2)-1.388(2) Å. Analysis of the
crystal packing shows that most of the contacts correspond to
C–H…πi and C–H…H interactions.
The principal result is that 8-substituted probes 7, 8, and 9
exhibit a typical Bodipy-like absorption profile, with a strong
absorption band at 498 nm, 517 nm and 521 nm, respectively.
Probes 7–9 have high molar absorption coefficients in the range
of 8.1 × 104 – 10.0 × 104 M−1cm−1. The fluorescence spectra of
compounds 7–9 show a low-intensity broad emission band at
514 nm, 543 nm, and 547 nm. Advantages of probe 8 are that it
exhibits large Stokes shift (1061 cm-1), which is consistent with
decreased self-quenching, and ensures a low measurement
error of the excitation light and scattered light. The quantum
yields of bound free sensors 7–9 are low (Φ ≤ 0.01 in MeCN)
due to photoinduced electron transfer (PET) quenching of the
excited state of the boradiazaindacence moiety (electron
acceptor) by the lone pair on the nitrogen atom (electron donor)
of the amine moiety.33
In contrast, probes 11 and 12 containing receptor groups at the
positions 3 and 5 exhibit absorbance with a maximum at 613 nm
and 706 nm, respectively. These bands undergo a bathochromic
shift by ca. 100 and 200 nm compared to Bodipy 7–9 due to the
styryl extension at the positions 3 and 5. The molar absorption
coefficients of probes 11 and 12 are lower than the average
values (ε = 7.0 × 104 M−1cm−1 and 3.3 × 104 M−1cm−1). However,
the fluorescence spectra of compounds 11 and 12 display a low-
intensity broad emission band in the near-infrared region (λem
=
688 nm and 762 nm, respectively), associated with reduced
background signals and photoinduced damage to biological
samples.34 Probes 11 and 12 show high Stokes shifts, which are
almost two times different from each other (1779 cm-1 vs 1041
cm-1). Moreover, probes 11 and 12 exhibit low fluorescence (3.6
and 9.5%, respectively) most likely due to efficient ICT
quenching of the exited state of the Bodipy chromophore from
the electron-donating amino moiety.34
Figure 3. General view of compound
ellipsoids drawn at p = 50%.
8 (CCDC-1587629) with thermal
Detection of Al3+ using compound 8, 11, and 12
Photophysical properties
Investigations of the photophysical properties of probes 7–9, 11
and 12 in the presence of metal cations showed that probe 7
bearing the 2,6-H-Bodipy core and probe 9 deprived of acetyl
groups at the chelator are poorly efficient for Al3+ detection (the
data on their sensing ability are given in Supporting information).
These compounds have low selectivity for Al3+ in the presence of
Cu2+, Pb2+, Zn2+, Fe3+, and Cr3+ ions and exhibit moderate
fluorescence response. In contrast, compounds 8, 11, and 12
Probes 7-9, 11, and 12 were examined by absorption and
steady-state fluorescence spectroscopy in dry MeCN (water
content less than 5%). The photophysical data are summarized
in Table 1.
Table 1. Photophysical data for probes[a]
derived
from
kryptopyrrole
using
the
2-((2-(2-
[b]
acetoxyethoxy)ethyl)amino)ethyl acetate group hold promise for
the selective ratiometric UV-vis and fluorescence turn-on
detection of Al3+.
λabs
[nm]
ε
λem
[nm]
Φem
Stokes
Probe
[M-1cm-1]
[%]
shift [cm-1]
7
8
498
517
521
613
706
81129
93199
100000
70031
32999
514
547
544
688
762
<0.1
<0.1
<0.1
9.5
625
1061
811
Thus, upon the addition of Al3+ to 8 (15 μM in MeCN), the
intensity of the absorption maximum gradually decreased
following the formation of a new bathochromically shifted band
centered at 527 nm with an isosbestic point at 524 nm (Figure
4A). The molar absorption coefficient changes only slightly from
9.3 × 104 to 8.6 × 104 M−1cm−1 upon Al3+ binding. As shown in
Figure 3A, there is a linear response relationship of 8 toward Al3+
in the range of 4.5 – 15.0 μM. As shown in Figure 4A, the
response of 8 to Al3+ is fitted by a linear curve in the range of 4.5
– 15.0 μM.
9
11
12
1779
1041
3.6
[a]
[b]
Spectra were recorded in CH3CN at 298 K.
Quinine sulfate as the
reference Φ = 0.55 in 0.1 M H2SO4, λex = 310 nm.32 All Φem values are
corrected for changes in the refractive index.
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10.1002/ejoc.201900315
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Figure 4
.
Spectral characteristics. (A) Absorption spectra of the reaction solution of probe
8
(15 μM) in MeCN containing Al3+ at different concentrations.
Inset: The corresponding absorption at 527 nm as a function of the Al3+ concentration. (B) Fluorescence titration spectra (λex = 504 nm) of probe 8 (15 μM)
upon the addition of 1 equiv. of Al3+ in MeCN. Inset: The Job plot indicating the 1:1 stoichiometry of the complex formation. (C) Absorption spectra of the
reaction solution of probe 11 (15 μM) in MeCN containing Al3+ at different concentrations. Inset: The corresponding absorption at 573 nm as a function
of the Al3+ concentration. (D) Fluorescence titration spectra (λex = 580 nm) of probe 11 (15 μM) upon the addition of 1 equiv. of Al3+ in MeCN. Inset: The Job
plot indicating the 1:2 stoichiometry of the complex formation. (E) Absorption of the reaction solution of probe 12 (15 μM) in MeCN containing Al3+ at
different concentrations. Inset: The corresponding absorption at 627 nm and 583 nm as a function of the Al3+ concentration. (F) Fluorescence titration
spectra (λex = 640 nm) of probe 12 (15 μM) upon the addition of 2 equiv. of Al3+ in MeCN. Inset: The Job plot experiment.
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Compound 8 was studied as a fluorescent probe for the
same condition. Upon the addition of Al3+ to 8 (15 μM in MeCN,
λex = 504 nm), the quenching is disrupted by the coordination of
Al3+ by the amine moiety, and the solution of 8 shows intense
green fluorescence (Figure 4B). The maximum fluorescence
emission wavelengths are slightly shifted (547 nm) upon the
addition of Al3+, while strong fluorescence enhancement (~1200-
fold) is observed by the naked eye. The quantum yield of the
bound sensor is 0.18. A weakening of the fluorescence
spectrum of 8 was observed by titrating with Al3+ in an amount
greater than one equivalent per ligand. The Job plot confirmed
that probe 8 is able to complex Al3+ in a 1:1 ratio. The binding
affinity of probe 8 for Al3+ was quantified based on fluorescence
titration experiments, giving the association constant (Ks) of 3.2
103 M-1, which is in the range of those reported for Al3+ binding
chemosensors.35-37 Moreover, the limit of detection was as low
as 3.8 μM, suggesting that probe 8 has high sensitivity.
detection of Al3+ by means of fluorescence response under the
0.31). All these suggest that probe 12 undergoes a series of
reorganizations and oscillations (internal conversion, intersystem
crossing) before it reaches the ground state. A Job plot
experiment confirmed the complicate complexes formation and
provided evidence that probe 12 most likely is able to form a
complex with Al3+ in 1:1 and 1:2 ratios. The fluorescence
intensity linearly depends on the Al3+ concentration in the range
from 4.5 to 15.0 μM.
The fluorescence responses of 8, 11, and 12 to various cations
and their selectivity for Al3+ was examined (Figure 5). Significant
spectral changes for probe 8 are observed only in the case of
Al3+. Thus, the addition of Al3+ to probe 8 induces 1200-fold
fluorescence enhancement. Under the same conditions, the
addition of Cr3+ and Cu2+ resulted in only 90-fold and 340-fold
fluorescence enhancement, respectively (Figure 5A). Other
cations, such as Li+, Na+, K+,Ca2+, Ag+, Cd2+, Zn2+, Co2+, Fe2+,
Fe3+ , Pb2+, Hg2+, Mg2+, Mn2+, Ni2+, and Ba2+, which occur at high
concentrations under physiological conditions, have no influence
on fluorescence enhancement. To further explore the utility of 8
as an ion-selective fluorescent chemosensor for Al3+, we
performed competitive experiments in the presence of 1 equiv.
of Al3+ and a mixture of 10 equiv. excess of other metal cations;
there are no significant changes in the fluorescence intensity
compared with that measured in the absence of other metal ions
apart from 1 equiv. of Al3+.
The changes in the absorption spectrum of probe 11 upon the
addition of Al3+ ions are much more pronounced compared to
probe 8 (Figure 4C). The complexation with Al3+ causes a strong
hypsochromic shift of the absorption maximum of probe 11,
resulting in the change in the color from blue to purple. The band
at 613 nm decreases without a noticeable shift, and a strong
absorption band appears at 573 nm. The molar absorption
coefficient changes only slightly from 7.0 × 104 to 6.9 × 104
M−1cm−1 upon Al3+ binding. There is
a linear response
relationship of 11 toward Al3+ in the range of 1.5 – 7.5 μM. The
presence of clear isosbestic points at 583 nm confirms the
formation of a complex with a single stoichiometry. The changes
in the fluorescence spectra of 11 attest to the presence of an
incremental amount of Al3+ (Figure 4D). The turn-on
fluorescence response of probe 11 was observed for Al3+ with an
emission band at 591 nm. Upon the addition of Al3+ to probe 11
(15 μM in MeCN, λex = 580 nm), an intense orange fluorescence
increases 1000-fold (the quantum yield of the bound sensor is
0.34). The binding analysis using the Job plot suggested that the
1:2 complex of probe 11 with Al3+ is responsible for the observed
fluorescence enhancement. The stability constant of the 1:2
complex formed between Al3+ ions and compound 11 in
acetonitrile, as calculated from UV-Vis spectrophotometric
titrations, is logβ = 12.34. The limit of detection of probe 11 is up
to 1.6 μM.
Probe 11 was found to be less selective (Figure 5B). The
fluorescence intensity ratio IAl/ICr of probe 11 measured in the
presence of Al3+ and Cr3+ is 1:1, while the intensity ratios IAl/ICu
and IAl/IFe measured in the presence of Cu2+ and Fe3+ are 2 : 1
and 46 : 1, respectively. The treatment of probe 11 with other
metal ions even in 10 equiv. excesses resulted in no significant
changes. In contrast, Cu2+ and Fe3+ ions have no influence on
the fluorescence enhancement of probe 12 (Figure 5C).
Significant spectral changes for probe 12 are observed only in
the case of Al3+ and Cr3+. The fluorescence intensity ratio IAl/ICr
of probe 12 measured in the presence of Al3+ and Cr3+ is 1.7 : 1.
The fluorescence enhancement for probe 12 is not detected in
the presence of 10 equiv. excess of others metal cations, such
as Fe2+, Fe3+, Mg2+, Pb2+, Hg2+, Ni2+, Co2+, Zn2+, Cd2+, Ag+, Ba2+,
Ca2+,, Li+, Na+, and K+.
Mechanistic study
Upon the addition of Al3+ to probe 12, new peaks appear in the
absorption spectra at 627 nm and 583 nm accompanied by a
change in the color of the solution from green to reddish-blue
(Figure 4E). The absorption peak centered at 706 nm decreases
with the gradual addition of Al3+, and two isosbestic points at 684
nm and 646 nm are observed, which are indicative of the
stepwise formation of complexes of different stoichiometry. The
plot of the absorption intensity versus the Al3+ concentration
shows a good linear relationship in the range of 1.5 – 15.0 μM.
The fluorescence intensity of chemosensor 12 (15 μM in MeCN,
The 1H NMR titration analysis was used to investigate the
interaction mode between the sensor molecules and Al3+ (see
Supporting information). The chemical shifts of the protons in the
probe before and after the addition of Al3+ for the representative
probe 8 are depicted in Figure 6. In the presence of Al3+ (0 – 1.1
equiv.), the side-chain protons a,b,c,d, and e of probe 8 shifted
by about 0.4 – 0.6 ppm, which is accompanied by the signal
spreading. The resonance signals g and h for the phenyl ring at
6.94 ppm and 6.09 ppm are shifted to 7.67 ppm and 7.75 ppm,
respectively, thereby providing evidence that the nitrogen
attached to the phenyl ring is involved in the recognition of Al3+.
Surprisingly, the side-chain protons f were found to be invariant
λex
=
640 nm) gradually increases with increasing Al3+
concentration (Figure 4F). The intensity of red fluorescence at
652 nm increased about 1400-fold upon the addition of one
equivalent of Al3+ and reached the maximum enhancement at 2
equivalents of Al3+ (the quantum yield of the bound sensor is
f
to Al3+ addition, which excludes CH2 OAc from the chelating
groups.
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10.1002/ejoc.201900315
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μM) in MeCN, λex = 640 nm. Inset: The fluorescence response of probe 12 (15
μM) upon the simultaneous addition of Fe2+, Fe3+, Mg2+, Mn2+, Pb2+, Hg2+, Ni2+
,
Co2+, Zn2+, Cd2+ Ag+, Ba2+, Ca2+,, Li+, Na+, and K+ (150 μМ) and of probe 12
,
(15 μM) upon the addition of Al3+ (15 μM) and a mixture of other metal ions
(150 μM) in MeCN, λex = 640 nm.
Figure 6. 1H NMR titration plot of probe 8 with Al3+ in MeCN.
The HRMS (ESI, m/z) analysis was performed for a mixture of
probe 8 with 1 equiv of aluminum perchlorate hydrate. The peak
at m/z = 590.3478 [probe 8 + Al3+ - BF2 + H+]+ is clearly observed,
which confirmed the 1 : 1 metal-to-ligand recognition in the
detection process. In addition, there are peaks at m/z 691.9734
and 805.9814 assigned to the complex [probe 8 + Al3+ + 3H2O –
H+]+ and [probe 8 + Al3+ + 2ClO4 + H2O – BF2+ H+]+, respectively.
Thus, the probable binding mode of the 2-((2-(2-
acetoxyethoxy)ethyl)amino)ethyl acetate receptor group to six-
coordinated Al3+ ions is shown in Figure 7. Only two oxygen
atoms of the receptor group are involved in the coordination to
Al3+, while the terminal acetate groups create steric hindrance
required for selectivity. The coordination sphere of Al3+ is
completed with solution components, such as water, perchlorate
anion, acetonitrile, etc. This speculation is supported by poor
selectivity for Al3+ of probe 9 deprived of terminal acetyl groups
at the chelator (the data on probe 9 sensing ability are given in
Supporting information).
Figure 5. Fluorescence responses of 8, 11 and 12 to various cations. (A)
Fluorescence response of probe 8 (15 μM) upon the addition of Al3+ (15 μM)
and other metal ions (15 μM) in MeCN, λex = 504 nm. Inset: The fluorescence
Figure 7. Proposed binding mode of probes to Al3+
.
response of probe 8 (15 μM) upon the simultaneous addition of Fe2+, Fe3+
Mg2+, Mn2+, Pb2+, Hg2+, Ni2+, Co2+, Zn2+, Cd2+ Ag+, Ba2+, Ca2+,, Li+, Na+, and
,
,
K+ (150 μМ) and of probe 8 (15 μM) upon the addition of Al3+ (15 μM) and a
mixture of other metal ions (150 μM) in MeCN, λex = 504 nm. (B) Fluorescence
response of probe 11 (15 μM) upon the addition of Al3+ (15 μM) and other
metal ions (15 μM) in MeCN, λex = 580 nm. Inset: The fluorescence response
Conclusions
of probe 11 (15 μM) upon the simultaneous addition of Fe2+, Mg2+, Mn2+, Pb2+
,
In summary, we synthesized and characterized five novel
pseudo-crown-based sensor molecules, which show a turn-on
response for Al3+. The exploration of the structure–function
relationship to functionalized Bodipy dyes shows that probe 7
Hg2+, Ni2+, Co2+, Zn2+, Cd2+, Ag+, Ba2+, Ca2+,, Li+, Na+, and K+ (150 μМ) and of
probe 11 (15 μM) upon the addition of Al3+ (15 μM) and a mixture of other
metal ions (150 μM) in MeCN, λex = 580 nm. (C) Fluorescence response of
probe 12 (15 μM) upon the addition of Al3+ (15 μM) and other metal ions (15
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chromatography (TLC) (petroleum ether–ethyl acetate, 1:1 v/v). After
cooling to room temperature, the reaction mixture was filtered and the
filtrate was extracted with ethyl acetate (3×60 mL). The organic extract
was dried over Na2SO4 and the solvent was removed under reduced
pressure. The residue was purified by silica gel column chromatography
using petroleum ether–ethyl acetate (1:1 → 1:10 v/v) as the eluting
solvent to obtain the product as a colorless oil (4.6 g, 73% yield). 1H NMR
(300 MHz, CDCl3): δ 3.54-3.81 (m, 13H), 4.10-4.36 (br.s, 1H, OH), 6.68-
6.71 (m, 3H), 7.19-7.27 (2H, m).42 MS (EI) 225 [M]+.
bearing the 2,6-H-Bodipy core and probe 9 deprived of acetyl
groups at the chelator are poorly efficient for Al3+ detection.
Meanwhile,
probe
8
bearing
the
2-((2-(2-acetoxyethoxy)ethyl)amino)ethyl acetate group can be
used mainly in fluorescence studies, whereas probes 11 and 12
enable a sensing response through two different channels – UV-
Vis and fluorescence. The maximum fluorescence intensity
enhancement for probes 8, 11, and 12 was achieved
ratiometrically by the addition of 0.5 – 2 equivalents of Al3+ ions,
while the limits of detection were found to be low. The observed
color change or enhanced fluorescence emission can be
attributed to the binding of Al3+ to the 2-((2-(2-
acetoxyethoxy)ethyl)amino)ethyl acetate moiety, which reduces
the electron-donating ability of the nitrogen atom conjugated to
the Bodipy core. Probes 8, 11, and 12 remain silent in the
presence of numerous alkali and alkaline earth metal ions,
including biologically essential Mg2+, Ca2+, and Fe3+. This
sensing behavior is highly selective and complex
absorption/emission maxima are higher than the average
values.38-40 Thus, our sensor molecules can be used for the
ratiometric detection of Al3+ in analytical samples in acetonitrile,
just as the 2-((2-(2-acetoxyethoxy)ethyl)amino)ethyl acetate
chelator can find application as a readily available chelator for
the development of Al3+-selective fluorescent probes.
Synthesis of 2-{[2-(2-acetoxyethoxy)ethyl](phenyl)amino}ethyl acetate (3).
Acetic anhydride (6.4 mL, 67.76 mmol) was added dropwise to a solution
of 2-{[2-(2-hydroxyethoxy)ethyl]phenylamino}ethanol (4.6 g, 20.44 mmol)
and pyridine (5.2 mL, 64.50 mmol) in CH2Cl2 (20 mL) with cooling in an
ice bath. The reaction mixture was stirred for 20 h at r.t. The reaction was
monitored by TLC (petroleum ether–ethyl acetate, 1:1 v/v). The mixture
was diluted with CH2Cl2 (20 mL) and washed with water (3×20 mL). The
organic layer was dried over Na2SO4. The solvent was removed under
reduced pressure. The crude product was purified by silica gel column
chromatography using petroleum ether–ethyl acetate (1:1 → 1:10 v/v) as
the eluting solvent to obtain the product as a viscous oil (4.4 g, 71%
yield). 1H NMR (300 MHz, CDCl3): δ 2.04 (s, 3H), 2.07 (s, 3H), 3.56-3.67
(m, 8H), 4.18-4.28 (m, 4H), 6.72-6.78 (m, 3H), 7.23-7.27 (m, 2H).30 MS
(EI) 309 [M]+.
Synthesis of 2-{[2-(2-acetoxyethoxy)ethyl](4-formylphenyl)amino}ethyl
acetate (4). Phosphorous oxychloride (0.29 mL, 3.10 mmol) was added
dropwise with stirring to dry DMF (1.5 mL) at 0 oC. The resulting mixture
was stirred at r.t. for
1
h. Then
a
solution of 2-{[2-(2-
acetoxyethoxy)ethyl](phenyl)amino}ethyl acetate (3.0 g, 9.71 mmol) in
dry DMF (1 mL) was added. The mixture was heated at 90 C for 2 h,
cooled and then poured onto crushed ice in a beaker. A saturated
solution of sodium acetate was added dropwise to adjust the pH value to
7. The mixture was extracted with ethyl acetate (3×50 mL) and dried over
Na2SO4. The solvent was removed under reduced pressure. The crude
product was purified by column chromatography using petroleum ether–
ethyl acetate (1:1 v/v) as the eluting solvent. The product was obtained
as a viscous colorless oil (2.9 g, 89% yield). 1H NMR (300 MHz, CDCl3):
δ 2.04 (s, 3H), 2.05 (s, 3H), 3.63-3.69 (m, 6H), 3.74 (d, J = 6.4 Hz, 2H),
4.19-4.23 (m, 2H), 4.29 (t, J = 6.4 Hz, 2H), 6.81 (d, J = 8.9 Hz, 2H), 7.74
(d, J = 8.9 Hz, 2H), 9.75 (s, 1H, CHO).30 MS (EI) 337 [M]+.
Experimental Section
General information
All chemicals and reagents were obtained from commercial sources and
used as-received, unless otherwise noted. Toluene, acetonitrile (MeCN),
and dichloromethane (CH2Cl2) were dried and purified under nitrogen
using standard methods41 and were distilled immediately before use. The
structures of the compounds were established by 1D and 2D NMR (1H,
13C, 19F, 11B) spectroscopy. The NMR spectra were acquired on a Bruker
Avance 600 spectrometer at room temperature; the chemical shifts δ
were measured in ppm relative to the solvent signals (1Н: CDCl3, δ =
7.27 ppm; CD3CN, δ = 1.94 ppm; 13C: CDCl3, δ = 77.00 ppm; CD3CN, δ
= 118.26 ppm). Splitting patterns are designated as s, singlet; d, doublet;
t, triplet; q, quartet; m, multiplet. The coupling constants (J) are in Hertz.
Synthesis
acetoxyethyl)aminophenyl]-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-
indacene (7). 4-((2-(2-Acetoxyethoxy)ethyl)(2-
of
4,4-difluoro-8-[4-(2-(2-acetoxyethoxy)ethyl)(2-
Accurate
high-resolution
mass
spectra
were
obtained
on
acetoxyethyl)amino)benzaldehyde (200 mg, 0.59 mmol) and 2,4-
dimethylpyrrole (0.13 mL, 1.26 mmol) were dissolved in anhydrous
CH2Cl2 (18 mL) under argon atmosphere. One drop (5μl) of trifluoroacetic
acid was added, and the solution was stirred at room temperature
overnight. A solution of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (148
mg, 0.65 mmol) in anhydrous CH2Cl2 (23 mL) was added using a syringe,
and the stirring was continued for another 12 h. After the addition of
triethylamine (3.56 mL), BF3·OEt2 (3.56 mL) was gradually added during
20 min in an ice-water bath followed by continuous stirring at room
temperature overnight. The reaction solution was shaken with 5%
aqueous sodium bicarbonate (60 mL). The organic layer was washed
with water (3×30 mL), passed through a Celite pad, dried over anhydrous
sodium sulfate, and concentrated in vacuo. The residue was twice
purified by flash chromatography (CH2Cl2 to CH2Cl2/MeOH = 100:5) to
obtain a red solid substance (17 mg, 5% yield) with m.p.102-105 оС. 1H
NMR (400 MHz, CDCl3): δ 1.52 (s, 6H, 3,5-CH3), 2.08 (s, 3H, CH3CO),
2.11 (s, 3H, CH3CO), 2.57 (s, 6H, 1,7-CH3), 3.65 (t, 2H, CH2, J = 5.8 Hz),
3.68-3.73 (m, 6H, CH2O, CH2N), 4.24-4.25 (m, 2H, CH2), 4.31 (t, 2H,
CH2OAc, J = 6.5 Hz), 5.89 (s, 2H, 2,6-CH), 6.87 (d, 2H, CHAr, J = 8.7 Hz),
BrukermicrOTOF-QTM ESI-TOF (Electrospray Ionization/Time of Flight)
and Thermo Scientific* LTQ Orbitrap mass spectrometers. EI mass
spectra were recorded on a Finnigan MAT Incos 50 spectrometer (70 eV).
Analytical thin-layer chromatography (TLC) was carried out on silica gel
plates (silica gel 60 F254 aluminum-supported plates); the visualization
was accomplished with an UV lamp (365 nm). Column chromatography
was performed on neutral aluminum oxide (Brockmann II, pH 9-10) or
silica gel 60 (230-400 mesh). UV-Vis absorption spectra and steady-state
fluorescence emission spectra were obtained with
a Panorama
instrument at the IOC RAS using 3-mL quartz cuvettes with a path length
of 1 cm. The measurements were performed in air atmosphere in
acetonitrile.
Synthesis of 2-{[2-(2-hydroxyethoxy)ethyl]phenylamino}ethanol (2).
A
mixture of 2-anilinoethanol (4.0 g, 29.22 mmol), 2-(2-
chloroethoxy)ethanol (6.0 g, 48.46 mmol), CaCO3 (5.0 g, 50.0 mmol),
and KI (0.48 g, 2.24 mmol) in water (60 mL) was refluxed with vigorous
stirring for 15 h. The progress of the reaction was monitored by thin-layer
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900315
European Journal of Organic Chemistry
FULL PAPER
7.09 (d, 2H, CHAr, J = 8.7 Hz). 13C NMR (125 MHz, CDCl3): δ 14.5, 14.7,
20.9, 49.9, 51.1, 61.1, 63.4, 68.4, 69.2, 112.4 (CHAr), 120.9 (CH), 123.1,
129.1 (CHAr), 132.1, 142.7, 143.1, 147.7, 154.9, 171.9 (C=O). 19F NMR
added using a syringe, and the stirring was continued for another 20 min.
After the addition of triethylamine (12 mL), BF3·OEt2 (12 mL) was
gradually added during 10 min in an ice-water bath followed by
continuous stirring at room temperature for 1 h. The reaction solution was
washed with 5% aqueous sodium bicarbonate (2×50 mL). The organic
layer was washed with water (3×100 mL), passed through a Celite pad,
dried over anhydrous sodium sulfate, and concentrated in vacuo. The
residue was purified by flash chromatography (petroleum ether to
petroleum ether/CH2Cl2 = 1:2) to obtain a red solid substance (720 mg,
40% yield). 1H NMR (300 MHz, CDCl3): δ 1.00 (t, 6H, CH3CH2, J = 7.3
Hz), 1.30 (s, 6H, 3,5-CH3), 2.32 (q, 4H, CH3CH2, J = 7.3 Hz), 2.54 (s, 6H,
1,7-CH3), 7.29-7.31 (m, 2H), 7.48-7.50 (m, 3H).43 MS (ESI) 380 [M]+.
1
(282 MHz, CDCl3): δ -146.3 (q, JF-B = 38.0 Hz, 2F). 11B NMR (96 MHz,
CDCl3):
C26H36BF2N3O5Na, 578.2613; found, 578.2616.
δ 0.78 (t, J =
38.0 Hz). HRMS: calcd [M+Na]+ for
Synthesis
acetoxyethyl)aminophenyl]-2,6-diethyl-1,3,5,7-tetramethyl-4-bora-3a,4a-
diaza-s-indacene (8). 4-((2-(2-Acetoxyethoxy)ethyl)(2-
of
4,4-difluoro-8-[4-(2-(2-acetoxyethoxy)ethyl)(2-
acetoxyethyl)amino)benzaldehyde (500 mg, 1.48 mmol) and 3-ethyl-2,4-
dimethyl-1H-pyrrole (0.42 mL, 3.12 mmol) were dissolved in anhydrous
CH2Cl2 (46 mL) under argon atmosphere. One drop (5μl) of trifluoroacetic
acid was added, and the solution was stirred at room temperature
overnight. A solution of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (370
mg, 1.63 mmol) in anhydrous CH2Cl2 (65 mL) was added using a syringe,
and the stirring was continued for another 5 h. After the addition of
triethylamine (9 mL), BF3·OEt2 (9 mL) was gradually added during 30 min
in an ice-water bath followed by continuous stirring at room temperature
overnight. The reaction solution was shaken with 5% aqueous sodium
bicarbonate (150 mL), and the mixture was passed through a Celite pad
and washed with CH2Cl2 (80 mL) to remove the black solid. The organic
layer was washed with water (3×30 mL), passed through a Celite pad,
dried over anhydrous sodium sulfate, and concentrated in vacuo. The
residue was twice purified by flash chromatography (CH2Cl2 to
CH2Cl2/MeOH = 100:1) to obtain a red solid substance (382 mg, 42%
yield) with m.p.126-129 оС. 1H NMR (300 MHz, CDCl3): δ 1.01 (t, 6H,
CH3CH2, J = 7.2 Hz), 1.41 (s, 6H, 3,5-CH3), 2.08 (s, 3H, CH3CO), 2.11 (s,
3H, CH3CO), 2.33 (q, 4H, CH3CH2, J = 7.2 Hz), 2.54 (br. s, 6H, 1,7-CH3),
3.61-3.75 (m, 8H, CH2O, CH2N), 4.25 (t, 2H, CH2OAc, J = 4.8 Hz), 4.31 (t,
2H, CH2OAc, J = 6.6 Hz), 6.84 (d, 2H, CHAr, J = 8.8 Hz), 7.08 (d, 2H,
CHAr, J = 8.8 Hz). 13C NMR (75 MHz, CDCl3): δ 12.1, 12.6, 14.7, 17.2,
21.0, 49.2, 51.1, 61.4, 63.6, 68.6, 69.3, 112.2 (CHAr), 123.7, 129.4, 129.5
Synthesis
acetoxyethyl)amino)styryl)-2,8-diethyl-5,5-difluoro-1,3,9-trimethyl-10-phe-
nyl-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide (11).
of
(E)-7-(4-((2-(2-acetoxyethoxy)ethyl)(2-
A
mixture of aldehyde 4 (266 mg, 0.79 mmol), Bodipy 10 (100 mg, 0.26
mmol), piperidine (0.15 mL, 1.52 mmol), and acetic acid (0.15 mL, 2.63
mmol) in dry toluene (18 mL) was refluxed for 12 h using a Dean-Stark
apparatus. After cooling down to ambient temperature, the solvent was
distilled off under reduced pressure and the residue was purified three
times by column chromatography (petroleum ether to petroleum
ether/ethyl acetate = 2:1) to obtain a green solid substance (78 mg, 43%
yield) with m.p.125-127 оС. 1H NMR (300 MHz, CDCl3): δ 1.01 (t, 3H,
CH3CH2, J = 7.5 Hz), 1.16 (t, 3H, CH3CH2, J = 7.4 Hz), 1.30 (s, 3H, CH3),
1.32 (s, 3H, CH3), 2.07 (s, 3H, CH3), 2.10 (s, 3H, CH3), 2.29 (q, 2H,
CH3CH2, J = 7.5 Hz), 2.59 (s, 3H, CH3), 2.60 (q, 2H, CH3CH2, J = 7.4 Hz),
3.64-3.72 (m, 8H, CH2O, CH2N), 4.22-4.25 (m, 2H), 4.29 (t, 2H, CH2, J =
6.3 Hz), 6.78 (d, 2H, J = 8.7 Hz), 7.19 (d, 1H, J = 16.6 Hz), 7.30-7.33 (m,
2H), 7.48-7.53 (m, 5H), 7.60 (d, 1H, J = 16.6 Hz). 13C NMR (75 MHz,
CDCl3): δ 11.4, 11.6, 12.7, 14.0, 14.6, 17.1, 18.4, 20.9, 29.7, 50.3, 51.4,
61.2, 63.5, 68.5, 69.3, 112.6, 116.5, 127.1, 128.5, 128.6 (CHAr), 128.7
(CH), 128.8 (CHAr), 129.0 (CHAr), 129.2 (CHAr), 131.5, 132.0, 133.0,
135.3, 135.7, 136.1, 137.9, 138.6, 138.7, 147.3, 150.4, 153.8, 170.8,
170.9. 19F NMR (282 MHz, CDCl3): δ -142.5 (q, 1JF-B = 33.6 Hz, 2F). 11B
NMR (96 MHz, CDCl3): δ 1.05 (t, J =33.6 Hz). HRMS: calcd [M]+ for
C40H48BF2N3O3, 699.3656; found, 699.3660.
(CHAr), 131.6, 132.6, 138.6, 141.2, 147.9, 148.8, 153.2, 171.0 (C=O). 19
F
1
NMR (282 MHz, CDCl3): δ -146.6 (q, JF-B = 35.4 Hz, 2F). 11B NMR (96
MHz, CDCl3):
C33H44BF2N3O5Na, 634.3237; found, 634.3240.
δ 0.86 (t, J
=35.4 Hz). HRMS: calcd [M+Na]+ for
Synthesis
of
4,4-difluoro-8-[4-(2-(2-ethoxy)ethyl)(2-
Synthesis
of
3,7-bis((E)-4-((2-(2-acetoxyethoxy)ethyl)(2-
acetoxyethyl)aminophenyl]-2,6-diethyl-1,3,5,7-tetramethyl-4-bora-3a,4a-
diaza-s-indacene (9). A solution of LiOH (5 mg, 0.21 mmol) in water (0.4
mL) was added to a solution of compound 8 (61 mg, 0.10 mmol) in
THF/MeOH (0.4:1.6 mL) under argon atmosphere. The resulting mixture
was stirred at room temperature for 12 h and the solvent was removed
under reduced pressure. The residue was twice purified by column
chromatography (CH2Cl2 to CH2Cl2/MeOH = 100:1) to obtain a red solid
substance (43 mg, 78% yield) with m.p.78-81 оС. 1H NMR (300 MHz,
CD3CN): δ 1.01 (t, 6H, CH3CH2, J = 7.5 Hz), 1.46 (s, 6H, 3,5-CH3), 2.33
(q, 4H, CH3CH2, J = 7.5 Hz), 2.48 (br. s, 6H, 1,7-CH3), 3.52-3.73 (m, 12H,
CH2O, CH2N), 6.92 (d, 2H, CHAr, J = 8.9 Hz), 7.08 (d, 2H, CHAr, J = 8.9
Hz). 13C NMR (75 MHz, CD3CN): δ 11.2, 11.7, 13.9, 16.5, 50.9, 53.8,
59.1, 60.9, 68.1, 72.5, 112.3 (CHAr), 120.3, 122.1, 128.9, 129.0 (CHAr),
131.7, 132.7, 138.9, 142.3, 148.7, 148.8, 153.8. 19F NMR (282 MHz,
CD3CN): δ -145.0 (q, 1JF-B = 35.6 Hz, 2F). 11B NMR (96 MHz, CD3CN): δ
0.73 (t, J =35.6 Hz). HRMS: calcd [M+Na]+ for C29H40BF2N3O3Na,
550.3028; found, 550.3023.
acetoxyethyl)amino)styryl)-2,8-diethyl-5,5-difluoro-1,9-dimethyl-10-phe-
nyl-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide (12). Was
obtained as a by-product in synthesis of compound 11. The product was
twice purified by column chromatography (petroleum ether to petroleum
ether/ethyl acetate = 2:1) to obtain a deep-blue solid substance (42 mg,
16% yield) with m.p.98-100 оС. 1H NMR (300 MHz, CD3CN): δ 1.14 (t, 6H,
2×CH3CH2, J = 7.4 Hz), 1.33 (s, 6H, 2×CH3), 1.99 (s, 6H, 2×CH3), 2.00 (s,
6H, 2×CH3), 2.58-2.69 (m, 4H, 2×CH3CH2), 3.62-3.66 (m, 16H, CH2O,
CH2N), 4.13-4.14 (m, 4H), 4.24 (t, 4H, 2×CH2, J = 6.1 Hz), 6.80-6.90 (m,
4H), 7.38-7.54 (m, 13H). 13C NMR (75 MHz, CDCl3): δ 11.4, 14.0, 18.4,
20.8, 50.1, 51.4, 53.3, 61.4, 63.4, 68.7, 69.3, 112.1, 112.2, 116.4, 116.7,
126.8, 128.6, 128.7, 128.9 (CHAr), 129.0 (CHAr), 129.3, 133.4, 135.5,
146.6, 147.7, 170.8, 170.9. 19F NMR (282 MHz, CDCl3): δ -139.6-139.0
(m, 2F). 11B NMR (96 MHz, CDCl3): δ 0.98-1.64 (m). HRMS: calcd [M]+
for C57H69BF2N4O10, 1018.5079; found, 1018.5076.
UV-Vis measurements
Synthesis of 4,4-difluoro-2,6-diethyl-1,3,5,7-tetramethyl-8-phenyl-4-bora-
3a,4a-diaza-s-indacene (10). Benzaldehyde (0.48 mL, 4.71 mmol) and 3-
ethyl-2,4-dimethyl-1H-pyrrole (1.38 mL, 10.24 mmol) were dissolved in
anhydrous CH2Cl2 (46 mL) under argon atmosphere. One drop (15μl) of
trifluoroacetic acid was added, and the solution was stirred at room
Probes 7-9, 11, and 12 (0.015 mmol) were dissolved in MeCN (3 mL).
The receptor (9 μL, 5 mM) was diluted in MeCN (2.991 mL) to the make
the final concentration equal to 15 μM. Then a solution of Al(ClO4)3•9H2O
(11.25 mg, 0.023 mmol) in MeCN (3.0 mL 7.69 mM) was added to a
solution of the probe (3 mL, 15 μM). The mixture was stirred, and the UV-
Vis spectra were recorded at room temperature.
temperature overnight.
A solution of 2,3-dichloro-5,6-dicyano-1,4-
benzoquinone (1.18 g, 5.20 mmol) in anhydrous CH2Cl2 (120 mL) was
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900315
European Journal of Organic Chemistry
FULL PAPER
Fluorescence measurements
1/[Al3+]. The typical plots (1/(F-F0) vs 1/[Al3+]) are given in Supporting
Information Data were linearly fitted, and the Ks value was obtained from
the slope and the intercept of the line.
Probes 7-9, 11, and 12 (0.015mmol) were dissolved in MeCN (3mL). The
receptor (9 μL, 5mM) was diluted in MeCN (2.991 mL) to make the final
concentration equal to 15 μM. Then a solution of Al(ClO4)3•9H2O (11.25
mg, 0.023 mmol) in MeCN (3.0 mL, 7.69 mM) was added to a solution of
the probe (3 mL, 15 μM). The mixture was stirred, and the fluorescence
spectra were recorded at room temperature.
The conditional stability constant value compound 11 was calculated
from the changes in the UV-Vis absorption spectra of the ligand over the
wavelength range 550–600 nm by using HypSpec.44,45
Determination of the limit of detection (LOD)
Quantum yield measurements
The limit of detection was calculated as described in the study.46 The
emission spectra of probes 8 and 11 (15 μM) in MeCN were collected for
30 times to determine the background noise σ. A linear regression curve
was fitted according to the emission intensity at 547 nm for 8 and 591 nm
for 11 as a function of the Al3+ concentrations in the range of 0 - 30 μM,
and the slope of the curve was obtained. The limit of detection was then
determined as the 3σ/slope.
Each quantum yield was measured three times (in different solutions).
The sample concentrations were chosen to obtain the absorbance of ca.
0.01. The relative quantum efficiencies were determined by comparing
the areas under the corrected emission spectra. Quinine sulfate (ΦF =
0.55 in 0.1M H2SO4) was used as the standard. In all ΦF determinations,
the correction for the solvent refractive index (η) was applied.
Measurements were performed in MeCN (spectrophotometric grade).
2
The equation Φx = Φst (Ix/Ist) × (Ast/Ax) × (ηx /ηst2) was used to calculate
the quantum yield of the sample, where Φst is the reported quantum yield
of the standard, I is the integrated emission spectrum in the cm–1 scale, A
is the absorbance at the excitation wavelength, and η is the refractive
index of the solvents used; the x subscript denotes unknown and st
denotes standard.
Acknowledgments
This work was financially supported by the Russian Foundation
for Basic Research and the Moscow City Government within the
framework of research projects No. 15-34-70030 “mol_а_mos”
and No. 17-53-16012.
Preparation of fluorometric and UV-Vis titration solutions
Stock solution (7.70 mM) of different perchlorate salts, including those of
Keywords: pseudo-crown, aluminum(III) ions, fluorescent probe,
Li+, Na+, K+, Ca2+, Ag+, Cd2+, Zn2+, Co2+, Fe3+, Pb2+, Mg2+, Ni2+, Ba2+, Al3+
,
Bodipy
Cu2+, Cr3+, and probes 7-9, 11, and 12 (5 mM) were prepared in dry
MeCN. The UV-Vis titration to evaluate the sensitivity of probes was
carried out by the sequential addition of 5, 10, 15, 20, 25, 30, 35, 40, 45,
50, 60, 70, 80, and 100 mL aliquots of Al3+ solutions to solutions of the
probes (3 mL). The fluorescence spectroscopic titration to evaluate the
sensitivity of probes was carried out by the sequential addition of 2, 6, 10,
14, 16, 22, 30, 34, 38, 50, 60, 70, 80, and 100 mL aliquots of Al3+
solutions to solutions of the probes (3 mL). The fluorescence spectra
were recorded at room temperature at the appropriate excitation
wavelength (504 nm for probe 7, 504 nm for probe 8, 504 nm for probe 9,
580 nm for probe 11, 640 nm for probe 12).
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applications in medical sciences. Aluminium and medicine, Nova Science:
New York, 2009, 45–68.
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[3] C. Exley, Aluminum in Biological Systems. Encyclopedia of
Metalloproteins, Springer, New-York, 2013, 33-34.
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Lamberts, G. N. Hendy, M. E. De Broe Nephro, Dial. Transplant. 2000, 15
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539–546.
Job plot
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[8] B. Fairman, A. Sanz-Medel, P. Jones, E.H. Evans, Analyst 1998, 123,
699-703.
Probes 7-9, 11, and 12 (0.0027 mmol) were dissolved in MeCN (3 mL)
[0.9 mL]. Solutions of the probes (33.3, 30.0, 26.7, 23.3, 20.0, 16.7, 13.3,
10.0, 6.7, and 3.3 μL) were taken and transferred to vials. The solution in
each vial was diluted with MeCN (2.967 mL). Al(ClO4)3•9H2O (1.32 mg,
0.0027 mmol) was dissolved in MeCN (3.0 mL, 0.9 mM). The resulting
solutions (0, 3.3, 6.7, 10.0, 13.3, 16.7, 20.0, 23.3, 26.7, 30.0, 33.3 μL)
were added to the appropriate diluted probe solution. Each vial had a
total volume of 3 mL. After voltexing the vials for a few minutes, UV-Vis
and fluorescence spectra were taken at room temperature.
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221.
[10] B. Valeur, I. Leray, Coord. Chem. Rev. 2000, 205, 3–40.
[11] A. Gupta, N. Kumar, RSC Adv. 2016, 6, 106413-10634.
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Park, C. Kim, J. Kim, Dyes Pigments 2013, 99, 1016-1021.
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Chem. 2017, 241, 1139–1144.
Determination of association constants Ks for the binding of Al3+ in probe
8 and stability constant (logβ) for 2 : 1 complex of compound 11 with Al3+
[14] S. H. Kim, H. S. Choi, J. Kim, S. J. Lee, D. T. Quang, J. S. Kim, Org. Lett.
2010, 12, 560-563.
The apparent association constants (Ks) for probe 8 - Al3+ complexes
were determined by the Benesi-Hildebrand equation 1/(F-F0) = 1/{Ks ×
(Fmax – F0) × [Al3+]} + 1/(Fmax – F0), where F is the fluorescence intensity
at 417 nm at any given Al3+ concentration, F0 is the fluorescence intensity
at 547 nm in the absence of Al3+, and Fmax is the maximum fluorescence
intensity at 547 nm in the presence of Al3+ in solution. The association
constant Ks was evaluated graphically by plotting 1/(F–F0) against
[15] D. Maity, T. Govindaraju, Chem. Comm. 2012, 48, 1039-1041.
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Dyes Pigments 2014, 101, 58-66.
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10.1002/ejoc.201900315
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10.1002/ejoc.201900315
European Journal of Organic Chemistry
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Novel chelating groups promising for
the design of Al3+-selective fluorescent
probes are proposed. A series of
Bodipy probes with pseudo-crown
based chelating groups was studied.
Fluorescence probes
Mikhail A. Kozlov, Denis Y. Uvarov,
Sergey A. Gorbatov, Natalya G.
Kolotirkina, Alexey D. Averin, Vadim V.
Kachala, Konstantin A. Lyssenko, Igor
V. Zavarzin, Yulia A. Volkova*
Some
probes
exhibited
good
selectivity to Al3+ among others alkali
and alkaline earth metal ions. The
high sensitivity of the probes with
detection limit of 1.6 - 3.8ꢀμM was
determined.
Page No. – Page No.
Pseudo-crown ethers as
а novel
scaffold for the development of Al3+-
selective fluorescent probes
This article is protected by copyright. All rights reserved.