New Polymerizable Tetraaza Macrocycle Containing Two Acridine Units for Selective Fluorescence Sensing of Metal Ions

Abstract

A new fluorescent bis(acridino)-macrocycle containing two allyl groups was synthesized and photophysically studied. Studies were carried out on metal ion recognition and selectivity-influencing effects including the determination of the relevant thermodynamic constants as logK and pKa. The proposed sensor molecule is recommended for the development of Zn²⁺-selective optochemical analyzers based on covalently immobilized ionophores as it has a unique pH-independent metal ion recognition ability, which is not influenced by anions and other potentially occurring metal ions in biological samples.

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https://doi.org/10.1007/s10895-021-02851-9
ORIGINAL ARTICLE
New Polymerizable Tetraaza Macrocycle Containing Two Acridine Units
forSelective Fluorescence Sensing ofMetal Ions
ÁdámGolcs1 · KorinnaKovács1· PannaVezse1· PéterHuszthy1· TündeTóth1,2
Received: 10 August 2021 / Accepted: 22 November 2021
© The Author(s) 2021
Abstract
A new fluorescent bis(acridino)-macrocycle containing two allyl groups was synthesized and photophysically studied.
Studies were carried out on metal ion recognition and selectivity-influencing effects including the determination of the
relevant thermodynamic constants as logK and pKa. The proposed sensor molecule is recommended for the development of
Zn2+-selective optochemical analyzers based on covalently immobilized ionophores as it has a unique pH-independent metal
ion recognition ability, which is not influenced by anions and other potentially occurring metal ions in biological samples.
Keywords Acridine· Metal ion recognition· Fluorescence sensor· Aza macrocycles
Introduction
Acridine and its derivatives have long been used as fluorophores.
A search in the Web of Science® database (setting keyword
acridine* results in more than 2400 hits in the titles and abstracts
of publications from the last 5years) confirms that acridines are
gaining increasing attention mostly in the fields of analytical
chemistry and fluorescence spectroscopy. The interest is still
unbroken nowadays, as numerous new sensor molecules
containing an acridine unit and their applications are reported
recently [1–5]. Most commonly, a 4,5-dimethyleneacridino-
or a 9-methyleneacridino-fluorophore is prepared from
the commercially available acridine and then coupled to
supramolecular receptor units in different ways [6–12]. Thus,
signaling is induced by an indirect electron transfer mechanism.
However, direct type acridino-sensor molecules containing
a fluorophore as a part of the receptor unit have also been
developed [13–16]. These acridino-crown ethers are most
commonly used as organic- and heavy metal cation sensors
[13–16]. In the case of environmental analyzers it is sufficient
to physically immobilize the ionophores. On the other hand,
covalent incorporation in membranes or various carrier phases
is essential for biological samples as in these cases perturbation-
free analysis is needed [17]. Covalent attachment generally
requires additional post-synthetic modifications of complex-
structured ionophores prepared by multi-step syntheses [18].
From this point of view, design of simple, easy-to-prepare and
covalently immobilizable sensor molecules are preferred.
Herein, we report a new directly polymerizable bis(acridino)-
macrocycle containing two allyl groups as a promising fluores-
cent sensor molecule for optochemical analysis of metal ions,
especially Zn2+ in biological samples. Preliminary studies on
molecular recognition and possible limitations of practical appli-
cation provide a valuable starting point for future development
of this type polymer-based sensors.
Results andDiscussion
Design andSynthesis oftheNew Fluorescent Sensor
Molecule
A directly polymerizable bis(allylamino)-ionophore con-
taining acridine fluorophore units as parts of the coordina-
tion sphere was designed for covalent immobilization. The
four nitrogens as nucleophile centers of the macrocycle
are responsible for coordinating the cationic guests during
molecular recognition. Moreover, the aromatic units can act
as π-bound-donors, while the 16-crown-4 type macrocyclic
* Ádám Golcs
golcs.adam@edu.bme.hu
1 Department ofOrganic Chemistry andTechnology,
Budapest University ofTechnology andEconomics, Szent
Gellért tér 4, 1111Budapest, Hungary
2 Institute forEnergy Security andEnvironmental Safety,
Centre forEnergy Research, Konkoly-Thege Miklós út 29-33,
1121Budapest, Hungary
/ Published online: 29 December 2021
Journal of Fluorescence (2022) 32:473–481
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1 3
cavity has an internal size comparable with several softly
electrophilic metal ions. The proposed host was obtained by
a simple 3-step synthetic procedure starting from acridine
(1) involving no chromatographic purification steps. The
intermediates (2 and 3) for macrocyclization were prepared
according to the reported method [19] and were reacted in
high-dilution-conditions as outlined in Scheme1.
The reported synthetic procedure is favorable due to its
simplicity and outstanding yield regarding the preparations of
macrocyclic sensors. Detailed procedure for preparation and
data of characterization are reported in SubsectionSynthesis
of 7,23-bis(prop-2-en-1-yl)-7,15,23,31-tetraazahepta-
cyclo[27.3.1.113,170.05,32.09,14.016,21.025,30]tetratriaco-
nta-1,3,5(32),9,11,13(34),14,16(21),17,19,25,27,29(33),30-
tetradecaene (4).
Spectral Properties oftheNew
Fluoroionophore
Initially, the spectral properties of new tetraaza-macrocycle 4
were investigated. The absorption and fluorescence emission
spectra of the sensor molecule are shown in Fig.1.
The absorption and emission peak-wavelengths were
251nm and 412nm, respectively. A large Stokes-shift of
161nm was observed. The absence of spectral overlap
reduces the possibility of self-absorption. The fluorescence
quantum yield was determined as 8.6 ×
10–4 in acetonitrile,
indicating a weak fluorescence of the free ligand.
Scheme1 Macrocyclization
of heterocyclic intermediates
to gain new polymerizable
fluoroionophore 4
Fig. 1 UV/Vis-absorption (left)
and fluorescence emission
(right, λexcitation = 249nm) spec-
tra of sensor molecule 4
Fig. 2 Studies on metal ion-selectivity of new fluoroionophore 4
(λexcitation = 249 nm, chost = 1 μM in acetonitrile, cmetal ions = 10μM in
water or ethanol in the case of Pd2+)
474 Journal of Fluorescence (2022) 32:473–481
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1 3
Studies onMetal Ion Selectivity
andComplexation
Studies on metal ion selectivity were performed by adding
10 equivalents of 23 different metal ions as 50mM aque-
ous solutions separately to the solution of macrocycle 4 in
acetonitrile (Fig.2).
Changes in fluorescence spectra indicated complex for-
mation with
Al3+, Pb2+, Cd2+, Zn2+ and Pd2+. These metal
ions caused a remarkable fluorescence enhancement in the
corresponding order. In the cases of the other 18 metal salts,
no spectral change was observed, indicating that complexa-
tion did not take place.
Fig. 3 Series of spectra for fluorescence titration of new ionophore 4 with aqueous solutions of A: Al3+, B: Pb2+, C: Cd2+, D: Zn2+ and ethanol
solution of E: Pd2+ (chost = 1μM in acetonitrile)
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In order to determine the stability constants of the com-
plexes, the host molecule was titrated with the aqueous solu-
tions of the 5 preferred metal ions. Results are shown in
Fig.3.
In the case of titration with Pd2+, a remarkable back-
ground emission was observed, which necessitated the cor-
rection of the results over the entire spectral range. Presuma-
bly it was caused by ethanol used as a solvent, which altered
the polarity of the medium during the titration experiment
(PdCl2 as a Pd2+ source is insoluble in water).
For determining the complex stability constants, non-
linear regression curves were globally fitted on the spec-
troscopic experimental data based on the least square’s
method. The results of these regression analyses on titration
experiments are shown in Fig.4.Based on the calculations,
1:1 complex stoichiometry was suggested in each case.
Results are summarized in Table1.
Among the preferred metal ions, the most stable com-
plexes were formed with
Zn2+, Cd2+ and Pb2+, respectively.
Similar stabilities are not surprising as these metal ions have
quite the same chemical character. The host formed a com-
plex of relatively weaker stability with Al3+ and Pd2+.
Studies onProtonation
New ionophore 4 is prone to accept protons in acidic
medium due to its weak basic character. Studies on protona-
tion are essential, since it can strongly influence optical sign-
aling. Moreover, the different ionization states also effect
Fig. 4 Non-linear functions as results of the applied global fitting
analyses (based on Eq.3 in SubsectionFluorescence measurements
and evaluation of the results) for calculating logK values in the cases
of the preferred ions of new fluorescent macrocycle 4 (Fobs refers to
the observed fluorescence signal upon addition of the corresponding
amount of metal ion, while F0 is the initial fluorescence of free host 4
in absence of metal ions)
Table 1 Logarithms of the
calculated K constants for
complexes of new ionophore 4
with preferred metal ions
Metal ion logK
Al3+ 5.00 ± 0.10
Pb2+ 5.50 ± 0.10
Cd2+ 5.60 ± 0.10
Zn2+ 5.70 ± 0.05
Pd2+ 3.60 ± 0.20
Fig. 5 Series of fluorescence spectra for acidifying new ionophore 4
(cionophore = 1μM in acetonitrile, λexcitation = 249nm)
Fig. 6 Non-linear regression curve to determine the pKa (based on
Eq.6 in Fluorescence measurements and evaluation of the results).
476 Journal of Fluorescence (2022) 32:473–481
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1 3
the metal ion recognition ability of the sensor molecule. For
characterizing the proton association ability of the new mac-
rocycle, its pKa was determined. Determination was carried
out in acetonitrile due to the poor water-solubility of the
ionophore. Nitric acid was gradually added to the solution
of macrocycle 4. The aliphatic nitrogen atoms of the iono-
phore were protonated immediately, while protonation of
the heteroaromatic ones took place gradually (Fig.5).The
bathochromic shift of the emission indicated the appearance
of a new molecular form.
Determination of pKa was also carried out according to
a non-linear global fitting using the least square’s method
(Fig.6).The pKa, which characterizes the deprotonation of
the heteroaromatic NH+ unit of the ionophore was found
as 9.73 ± 0.03 in acetonitrile. Studies showed, that the
protonation of only one heterocyclic unit took place and
the protonation of the second acridine unit began much
later. It suggests the formation of intramolecular stabilizing
interactions.
Studies onAnion‑Coordination
The pKa of the conjugate acid of the aliphatic tertiary amine
groups of the ionophore are above 8 (predicted by Che-
mAxon), which indicates that these aliphatic N-atoms are
mainly in their protonated forms in neutral aqueous medium.
Hence, studies on anion-coordination were carried out to
exclude the possibility of interference with several com-
monly occurring counterions. Furthermore, investigations
were also carried out on the anion-coordinating ability of
the triple-protonated macrocycle as its molecular recogni-
tion ability can strongly differ from that of the corresponding
double-positively charged or the neutral one. The mentioned
ionization forms are shown in Fig.7.
Various tetrabutylammonium (sterically shielded cat-
ion which cannot be complexed) salts of
H2PO4−, NO3−,
HSO4−, CH3COO−, F−, Cl−, Br− and I− in 50mM aque-
ous solutions were added to differently protonated iono-
phore 4 in an amount of 10 equivalents regarding to the
host (Fig.8).No significant spectral change was observed
in each case, indicating that complexation of anions did
not take place even in the protonated forms of the host
molecule.
Fig. 7 The protonated forms of ionophore 4 A: in a neutral water-ace-
tonitrile mixture (42+) and B: in an acidic water-acetonitrile mixture
at the end point of acid titration (43+)
Fig. 8 Studies on the anion-selectivity of double-protonated 42+ (A) and triple-protonated 43+ (B) of ionophore 4 (cionophore = 1 μM,
λexcitation = 249nm) in an acetonitrile-based semi-aqueous medium
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1 3
Conclusions
We have designed and synthesized a new fluorescent
bis(acridino)-macrocycle containing two allyl groups as
an optochemical sensor molecule. This host molecule was
obtained with a good yield by a simple three-step synthetic
procedure starting from acridine. Photophysical studies
showed a favorable large Stokes-shift. New ionophore 4 has
negligible fluorescence as a free ligand and gave a turn-on
optical response by adding Al3+, Pb2+, Cd2+, Zn2+ and Pd2+
among 23 metal ions. Studies on metal ion recognition estab-
lished the formation of stable complexes in the cases of Al3+,
Pb2+, Cd2+ and Zn2+ with a 1:1 stoichiometry. These preferred
metal ions can selectively be detected over a wide pH-range
as the different protonated states of the sensor molecule had
no significant effect on complexation. The presence of various
anions did also not influence the metal ion recognition. From
the aspect of practical application, the proposed sensor mol-
ecule can effectively be used in biological samples for analysis
of Zn2+ since in this case the occurrence of competing Al3+,
Pb2+ and Cd2+ is not expected. The host molecule contains two
allyl groups, which make it suitable for direct polymerization
or covalent immobilization. This structural property enables
various future applications.
Experimental
Chemicals andApparatus
Chemicals were purchased from Sigma-Aldrich Corporation
(USA, owned by Merck, Germany) and used without further
purification unless otherwise noted. Solvents were dried and
purified according to well established methods [20]. Alu-
minum oxide 60 F254 neutral type E (Merck, Germany)
plate was used for thin-layer chromatography (TLC). Melt-
ing point was taken on a Boetius micro-melting point appa-
ratus and is uncorrected. Infrared spectrum was recorded on
a Bruker Alpha-T FT-IR spectrometer (Bruker Corporation,
USA) using KBr pastilles. NMR spectra were recorded on
a Bruker 300 Avance spectrometer (Bruker Corporation,
USA; at 300MHz for 1H and at 75.5MHz for 13C spec-
tra). HRMS analysis was performed on a Thermo Velos Pro
Orbitrap Elite (Thermo Fisher Scientific, Germany) system.
The ionization method was ESI and operated in positive ion
mode. The protonated molecular ion peaks were fragmented
by CID at a normalized collision energy of 35–45%. Data
acquisition and analysis were accomplished with Xcalibur
software version 2.2 (Thermo Fisher Scientific, Germany).
UV/Vis spectra were recorded on a UNICAM UV4-100
spectrophotometer controlled by VIZION 3.4 software
(ATI UNICAM, UK). Fluorescence emission spectra were
recorded on a Perkin-Elmer LS 50B luminescent spectrom-
eter (PerkinElmer Inc., USA) and were corrected by FL
Winlab 3.0 spectrometer software (PerkinElmer Inc., USA).
Quartz cuvettes with path length of 1cm were used in all
cases.
Synthesis of7,23‑bis(prop‑2‑en‑1‑yl)‑7,15,23,31‑tetr
aazaheptacyclo[27.3.1.113,170.05,32.09,14.016,21.025,30]
tetratriaconta‑1,3,5(32),9,11,13(34),14,16(21),17,19
,25,27,29(33),30‑tetradecaene (4)
A mixture of secondary amine 3 [19] (416mg, 1.32mmol),
finely powdered anhydrous caesium carbonate (2136mg,
6.56mmol) and dry and pure DMSO (200mL) were stirred
vigorously under argon atmosphere at room temperature for
30min, then bromo-derivative 2 [19] (480mg, 1.32mmol)
in dry and pure DMSO (50mL) was added dropwise. The
temperature of the mixture was raised to 60°C and kept at
this temperature for 4days. Water (500mL) was added to
the reaction mixture, which was extracted with ethyl ace-
tate (4 × 500mL). The combined organic phase was shaken
with water (9
×
500mL) and then with saturated aqueous
sodium chloride solution (1
×
500mL) to remove DMSO.
The organic phase was dried over magnesium sulphate, fil-
tered and the solvent was evaporated under reduced pressure.
The crude product was recrystallized from methanol, then
from propane-2-ol to gain 4 (304mg, 44%) as dark yellow
crystals.
M.p. = 144 °C. Rf = 0.50 (Al2O3 TLC, propane-
2-ol:dioxane 1:5). 1H-NMR (CD3OD): δ [ppm]: 3.67 (d,
J = 6.1Hz, 4H); 4.99 (s, 8H); 5.33 (d, J = 10.4 Hz, 2H);
5.55 (d, J = 17.3 Hz, 2H); 6.18–6.26 (m, 2H); 7.32 (t,
J = 7.6Hz, 4H); 7.67–7.71 (m, 8H); 8.54 (s, 2H). 13C-NMR
(CD3OD): δ [ppm]: 53.93; 56.19; 116.77; 124.34; 127.23;
129.79; 132.08; 135.89; 144.29; 154.75. IR: νmax [cm−1]:
3040; 2956; 2924; 2853; 1676; 1640; 1617; 1534; 1452;
1261; 1171; 1106; 1021; 916; 759. HRMS: m/z = [MH+]:
521.2699, (Calcd. for C36H32N4, 520.2627).
Fluorescence Measurements andEvaluation
oftheResults
Spectroscopic measurements were carried out at room tem-
perature (25 ± 1°C). Polarizers were not applied. A 350nm
cut off type bandpass filter and 5nm excitation and emission
slits were used in the cases of titration experiments, while in
the other cases slits were 10nm. During spectrophotometric
titrations, the solutions were added with a Hamilton-syringe
to the acetonitrile solutions of the ligand. The results were
corrected with the background signal and the dilution effect
of the added solutions. OriginPro 8.6 (OriginLab Corp.,
478 Journal of Fluorescence (2022) 32:473–481
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1 3
USA) software was used for evaluation and visualization of
the spectroscopic results.
Relative quantum efficiencies were also determined in
acetonitrile according to a literature method [21] based on a
comparison with acridine as a standard [22]. The excitation
and emission spectra were recorded in the same conditions
and instrument settings as in the case of the standard. (The
excitation wavelength for the ionophore was chosen to be
249nm, because of better comparability with the fluoro-
phore subunit and the reference compound.) The following
equation was used for calculation:
where subscript i refers to the sample of the initial investi-
gated compound, while subscript r refers to the reference.
The
Φ
is the quantum yield, n is the respective refractive
index of the solvents, I is the fluorescence intensity,
𝜆ex
is
the excitation wavelength,
𝜆em
is the emission wavelength
and A is the absorbance.
In the cases of turn-on type optical response, the stability
constants of the complexes (K) were determined by global
non-linear regression analysis. For determination of the
complex stability constant based on the observed fluores-
cence enhancement upon complexation, the following equa-
tion was used [23]:
where F is the measured fluorescence intensity, I0 is the
intensity of the emission, Φ is the fluorescence quantum
yield, ε is the molar absorption coefficient, b is the opti-
cal path length, [X] is the molar concentration of species
X and kX is a constant referring to the optical properties of
species X.
In the case of a complex with 1:1 stoichiometry the
association constant can be calculated by the following
equation:
where the ratios of k parameters and Ka were left as floating
parameters during the fitting method. (In the absence of Ka,
k values also have to be initially set as floating parameters.
For determination of Ka values, ratios of fitted k values were
handled as constants.) Parameters F and F0 are wavelength-
dependent variables and [G] was set as a variable, too. F0
refers to the initial fluorescence intensity of the free host
molecule, kH is a constant referring to the optical proper-
ties of the free host molecule,
k0
H
is a constant referring to
the optical properties of the free host in the presence of
the preferred guest molecule, constant kHG describes the
(1)
Φ
i
Φ
r
=
n
2
i
n2
r
∙
∫∞
0Ii
(
𝜆ex,𝜆em
)
d𝜆em
∫∞
0
Ir
(
𝜆ex,𝜆em
)
d𝜆em
∙1−10−Ar(𝜆ex)
1−10−Ai(𝜆ex)
(2)
F=I0Φ𝜀b[X]=kX[X]
(3)
F
F0
=kH∕k
0
H+
(
kHG∕k
0
H
)
Ka
[G]
1
+
K
a
[G]
photophysical features of the complex, Ka is the associa-
tion constant and [G] is the concentration of the initial guest
molecules.
Global non-linear fitting was carried out similarly in
the case of complexes with 1:2 (host:guest) stoichiometry
based on the following equation:
where ΔFobs is the change in fluorescence during titration
steps, kΔHG = kHG—kH, [H]0 is the initial concentration of
the host, K1 is the association constant of the first step of the
complex formation equilibrium, while K2 is the association
constant of the second step of the complexation.
The described method for the complexes with a 2:1
(host:guest) stoichiometry was performed based on the
following mathematical formula:
where [G]0 is the initial concentration of the guest molecule
and [H] is the concentration of the free host molecules.
The studies of the complex stoichiometries were also
carried out applying the described global non-linear fitting
methods. The stoichiometries were determined based on
the deviations resulting from the parameter fitting accord-
ing to the least square’s method using the mentioned equa-
tions. Titration experiments were performed with careful
consideration of the relevant recommendations [24].
Determination of pKa values in non-aqueous medium
was carried out based on the following equation [25]:
where F is the measured fluorescence intensity, Fmax is the
fluorescence intensity at the starting point of acid titration,
[H+] refers to the proton concentration, n shows the number
of associated proton / molecules, Fmin is the fluorescence
intensity at the end point of acid titration, Kacid is the acid
dissociation constant of the investigated compound. Dur-
ing the fitting method, the n and the Kacid were defined as
floating parameters in the equation. The value of n proved
to be close to 1, thus it was set as a constant. Hence, based
on the known values of variable [H+] and the wavelength-
dependent variables F, Fmax, Fmin, parameter Kacid can be
determined.
During the calculation it was considered that the pro-
ton dissociation of nitric acid is strongly reduced in ace-
tonitrile compared to the estimated total dissociation of
protons in water. The pKa for nitric acid in acetonitrile is
(4)
Δ
Fobs =
kΔHG[H]0K1[G]+kΔHG2[H]0K1K2[G]
2
1+K
1
[G]+K
1
K
2
[G]2
(5)
Δ
Fobs =
kΔHG[G]0K1[H]+kΔHG2[G]0K1K2[H]
2
1+K
1
[H]+K
1
K
2
[H]2
(6)
F
=
Fmax[H
+
]
n
+FminKacid
K
acid
+ [H+]n
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1 3
10.6 [26]. The [H+] values in Eq.6 were corrected with the
degree of dissociation corresponding to the concentration
of nitric acid using the Ostwald’s dilution law.
Acknowledgements The authors express their thanks to Dániel Ster
for his valuable technical assistance during this work. Thanks to Dr.
Miklós Dékány for the HRMS measurement.
Authors’ Contributions Á. G.: Conceptualization, Methodology, Formal
analysis, Investigation, Writing—Original Draft; K. K.: Investigation,
Formal analysis, Visualization, Writing—Original Draft; P. V.: Inves-
tigation, Formal analysis, Visualization; P. H.: Writing—Review &
Editing, Supervision, Funding acquisition, Resources; T. T.: Writing—
Review & Editing, Supervision, Project administration.
Funding Open access funding provided by Budapest University of
Technology and Economics. The financial support of the National
Research, Development and Innovation Office (grant number:
K128473) is gratefully acknowledged.
Data Availability The datasets generated during and/or analysed dur-
ing the current study are available from the corresponding author on
reasonable request.
Declarations
Ethics Approval Not applicable.
Consent to Participate Not applicable.
Consent for Publication Not applicable.
Conflicts of Interest The authors declare no conflicts of interest. The
funding institution had no role in the design of the study; in the col-
lection, analyses, or interpretation of data; in the writing of the manu-
script and in the decision to publish the results.
Open Access This article is licensed under a Creative Commons Attri-
bution 4.0 International License, which permits use, sharing, adapta-
tion, distribution and reproduction in any medium or format, as long
as you give appropriate credit to the original author(s) and the source,
provide a link to the Creative Commons licence, and indicate if changes
were made. The images or other third party material in this article are
included in the article's Creative Commons licence, unless indicated
otherwise in a credit line to the material. If material is not included in
the article's Creative Commons licence and your intended use is not
permitted by statutory regulation or exceeds the permitted use, you will
need to obtain permission directly from the copyright holder. To view a
copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/.
References
1. Dai Q, Liu H, Gao C, Li W, Zhu C, Lin C, Tan Y, Yuan Z, Jiang
Y (2018) A one-step synthesized acridine-based fluorescent che-
mosensor for selective detection of copper (II) ions and living cell
imaging. New J Chem 42(1):613–618. https:// doi. org/ 10. 1039/
C7NJ0 3615A
2. Lee SC, Park S, So H, Lee G, Kim KT, Kim C (2020) An Acridine-
based Fluorescent Sensor for Monitoring ClO− in Water Samples
and Zebrafish. Sensors 20(17):4764–4776. https:// doi. org/ 10. 3390/
s2017 4764
3. Totland C, Thomas PJ, Holst B, Akhtar N, Hovdenes J, Skodvin T
(2020) 9-Acridinemethanamine and Acridine-9-Carboxaldehyde
as Potential Fluorescence Lifetime pH Indicators. J Fluoresc
30:901–906. https:// doi. org/ 10. 1007/ s10895- 020- 02564-5
4. Dimitrijevs P, Domracheva I, Arsenyan P (2020) Improved method
for the preparation of nonyl acridine orange analogues and utiliza-
tion in detection of cardiolipin. New J Chem 44(23):9626–9633.
https:// doi. org/ 10. 1039/ D0NJ0 2116D
5. Nunes MC, dos Santos Carlos F, Fuganti O, da Silva LA, Ribas
HT, Winnischofer SMB, Nunes FS (2020) A facile prepara-
tion of a new water-soluble acridine derivative and application
as a turn-off fluorescence chemosensor for selective detec-
tion of
Hg2+. J Fluoresc 30:235–247. https:// doi. org/ 10. 1007/
s10895- 020- 02489-z
6. Guo C, Sedgwick AC, Hirao T, Sessler JL (2021) Supramolecular fluo-
rescent sensors: an historical overview and update. Coord Chem Rev
427:213560–213587. https:// doi. org/ 10. 1016/j. ccr. 2020. 213560
7. Lee M, Jang YC, Den W, Kuo P (2014)Synthesis of Fluorogenic
Chemosensors for
Hg2+ Detection Using Naphthalimide Deriva-
tives. InGreen Catalysts for Energy Transformation and Emission
Control. American Chemical Society. Washington, DC, USApp.
49–69.https:// doi. org/ 10. 1021/ bk- 2014- 1184. ch003
8. dos Santos Carlos F, da Silva LA, Zanlorenzi C, Nunes FS (2020)
A novel macrocycle acridine-based fluorescent chemosensor
for selective detection of Cd2+ in brazilian sugarcane spirit and
tobacco cigarette smoke extract. Inorg Chim Acta 508:119634–
119641. https:// doi. org/ 10. 1016/j. ica. 2020. 119634
9. Visscher A, Bachmann S, Schnegelsberg C, Teuteberg T, Mata RA,
Stalke D (2016) Highly selective and sensitive fluorescence detec-
tion of
Zn2+ and Cd2+ ions by using an acridine sensor. Dalton Trans
45(13):5689–5699. https:// doi. org/ 10. 1039/ C6DT0 0557H
10. Wang C, Fu J, Yao K, Xue K, Xu K, Pang X (2018) Acridine-
based fluorescence chemosensors for selective sensing of Fe3+
and Ni2+ ions. Spectrochim Acta Part A Mol Biomol Spectrosc
199:403–411. https:// doi. org/ 10. 1016/j. saa. 2018. 03. 015
11. Lee HN, Kim HN, Swamy KMK, Park MS, Kim J, Lee H, Park
S, Yoon J (2008) New acridine derivatives bearing immobilized
azacrown or azathiacrown ligand as fluorescent chemosensors for
Hg2+ and Cd2+. Tetrahedron Lett 49(7):1261–1265. https:// doi.
org/ 10. 1016/j. tetlet. 2007. 11. 158
12. Wang Y, Hu X, Wang L, Shang Z, Chao J, Jin W (2011) A New
Acridine Derivative as a Highly Selective ‘off–on’ Fluorescence
Chemosensor for Cd2+ in Aqueous Media. Sens Actuators B
Chem 156(1):126–131. https:// doi. org/ 10. 1016/j. snb. 2011. 03. 083
13. Rapi Z, Bakó P, Keglevich G, Baranyai P, Kubinyi M, Varga O
(2014) Synthesis and recognition properties of α-D-glucose-based
fluorescent crown ethers incorporating an acridine unit. J Incl Phe-
nom Macrocycl Chem 80(3–4):253–261. https:// doi. org/ 10. 1007/
s10847- 014- 0384-8
14. Rednic MI, Hădade ND, Bogdan E, Grosu I (2015) Macrocycles
embedding phenothiazine or similar nitrogen and/or sulphur con-
taining heterocycles. J Incl Phenom Macrocycl Chem 81(3):263–
293. https:// doi. org/ 10. 1007/ s10847- 014- 0455-x
15. Móczár I, Huszthy P (2019) Optically active crown ether-based
fluorescent sensor molecules: a mini-review. Chirality 31(2):97–
109. https:// doi. org/ 10. 1002/ chir. 23031
16. Golcs Á, Ádám BÁ, Horváth V, Tóth T, Huszthy P (2020)Synthe-
sis, molecular recognition study and liquid membrane-based applica-
tions of highly lipophilic enantiopure acridino-crown ethers. In Prime
Archives in Molecular Sciences. Vide Leaf, Hyderabad, Indiapp. 1–24.
ISBN: 978–93–90014–20–0 (Available online: https:// videl eaf. com/
synth esis- molec ular- recog nition- study- and- liquid- membr ane- based-
appli catio ns- of- highly- lipop hilic- enant iopure- acrid ino- crown- ethers/)
17. Bühlmann P, Pretsch E, Bakker E (1998) Carrier-based ion-selec-
tive electrodes and bulk optodes. 2. ionophores for potentiometric
480 Journal of Fluorescence (2022) 32:473–481
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

1 3
and optical sensors.Chem Rev98(4):1593–1688.https:// doi. org/
10. 1021/ cr970 113
18. Voloshina NS, Kamalov GL (2014) Crown Ethers Immobilized on the
Surface of Polymer Materials and Silicas. Prot Met Phys Chem Surf
50(5):587–598. https:// doi. org/ 10. 1134/ S2070 20511 40501 89
19. Golcs Á, Kovács K, Vezse P, Tóth T, Huszthy P (2021) Acridino-
Diaza-20-Crown-6 Ethers: New Macrocyclic Hosts for Optochem-
ical Metal Ion Sensing. Molecules 26(13):4043–4062. https:// doi.
org/ 10. 3390/ molec ules2 61340 43
20. Riddick JA, Bunger WB, Sakano TK (1986)Organic solvents: physi-
cal properties and methods of purification. wiley-interscience: New
York, New York, USApp. 1344–1400. ISBN: 0471084670
21. Lakowicz JR (2006) Principles of fluorescence spectroscopy.
springer science+business media: New York, New York, USApp.
9–60. ISBN-10: 0–387–31278–1, ISBN-13: 978–0387–31278–1
22. Diverdi LA, Topp MR (1984) Subnanosecond Time-Resolved
Fluorescence of Acridine in Solution. J Phys Chem 88(16):3447–
3451https:// doi. org/ 10. 1021/ j1506 60a016
23. Thordarson P (2011) Determining Association Constants from
Titration Experiments in Supramolecular Chemistry. Chem Soc
Rev 40(3):1305–1323. https:// doi. org/ 10. 1039/ C0CS0 0062K
24. Schalley CA (2012)Analytical methods in supramolecular
chemistry. Wiley VCH., Weinheim, Germanypp. 1–844. ISBN:
978–3–527–32982–3
25. Baruah M, Qin W, Flors C, Hofkens J, Vallee RA, Beljonne D,
Van der Auweraer M, De Borggraeve WM, Boens N (2006) Sol-
vent and pH Dependent Fluorescent Properties of a Dimethylami-
nostyryl Borondipyrromethene Dye in Solution. J Phys Chem A
110(18):5998–6009. https:// doi. org/ 10. 1021/ jp054 878u
26. Kolthoff IM, Chantooni MK (1999) Dissociation constant, Ka,
and stability constant, K(HA2-), of the 1:1 homoconjugate of
sulfuric and nitric acids in acetonitrile at 298.1 K. Revised val-
ues.JChemEngData44(1):124–129.https:// doi. org/ 10. 1021/ je980 1922
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