Full text of DOI:10.1080/10610278.2018.1523409

Supramolecular Chemistry
ISSN: 1061-0278 (Print) 1029-0478 (Online) Journal homepage: http://www.tandfonline.com/loi/gsch20
Benzoisothiazole-1,1-dioxide-based synthetic
receptor for zinc ion recognition in aqueous
medium and its interaction with nucleic acids
Milan Jakubek, Zdeněk Kejík, Veronika Antonyová, Robert Kaplánek, David
Sýkora, Róbert Hromádka, Kateřina Vyhlídalová, Pavel Martásek & Vladimír
Král
To cite this article: Milan Jakubek, Zdeněk Kejík, Veronika Antonyová, Robert Kaplánek,
David Sýkora, Róbert Hromádka, Kateřina Vyhlídalová, Pavel Martásek & Vladimír Král
(2018): Benzoisothiazole-1,1-dioxide-based synthetic receptor for zinc ion recognition in
aqueous medium and its interaction with nucleic acids, Supramolecular Chemistry, DOI:
10.1080/10610278.2018.1523409
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SUPRAMOLECULAR CHEMISTRY
https://doi.org/10.1080/10610278.2018.1523409
ARTICLE
Benzoisothiazole-1,1-dioxide-based synthetic receptor for zinc ion recognition
in aqueous medium and its interaction with nucleic acids
Milan Jakubeka,b, Zdeněk Kejíkc, Veronika Antonyováb, Robert Kapláneka,b, David Sýkoraa, Róbert Hromádkab,d,
b,c
Kateřina Vyhlídalováa, Pavel Martásek
and Vladimír Krála,b
aDepartment of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Prague, Czech Republic,;
c
bBIOCEV, First Faculty of Medicine, Charles University, Czech Republic; Department of Pediatrics and Adolescent Medicine, First Faculty of
d
Medicine, Charles University and General University Hospital in Prague Ke Karlovu, Prague Czech Republic; C2P s.r.o. Jungmannova 101,
503 51 Chlumec nad Cidlinou, Czech Republic
ABSTRACT
ARTICLE HISTORY
Received 19 June 2018
Accepted 9 September 2018
Benzoisothiazole-1,1-dioxide-based synthetic receptor was prepared by two step synthesis in 92 %
overall yield. Its applicability for the determination of Zn(II) and interction with nucleic acids was
studied by absorption spectroscopy. Obtained data, specifically low limit of detection, 0.15 µM
(R2 = 0.9933), showed the high potential of the tested structure motif for the recognition and
determination of Zn(II) ions in aqueous media (water:DMSO; 99:1 (ν/ν)). Alone receptor displayed
orderly strongly RNA affinity. Value of LogK was 6.1 and 4.9 for its complex (1:1) with RNA and DNA,
respectively. Nevertheless, in presence of complexed Zn(II) ions, its DNA affinity (represent by K,
LogK = 5.7) strongly grow to near value obtained for its interaction with RNA. On the other hand, its
RNA affinity (LogK = 5.9) displayed not significantly change in the presence of complexed one.
KEYWORDS
Chelator; hydrazone; nucleic
acid; zinc ions
1. Introduction
These facts stimulate the development of various analy-
tical methods suitable for the determination of Zn(II) ions.
Currently, sophisticated analytical techniques including
inductively coupled plasma atomic emission or mass spec-
trometry and atomic absorption spectroscopy are exten-
sively used for the determination of Zn(II) in environmental
and biological samples (5–7). However, the mentioned
approaches require a sophisticated instrumentation, high
skill personnel and a tedious sample preparation. Therefore
new alternative analytical tools such as selective synthetic
receptors are intensely developed and studied. (8–18)
One promising structure building block for the con-
struction of specific receptors for transition metals such
as zinc is represented by benzoisothiazole-1,1-dioxide
derivatives. Their ability to form complexes with transi-
tion metals was described by Fernanda et al. and Frija
et al. (19, 20). Combination of benzoisothiazole-1,1-
dioxide with selected structural motifs such as enamine
nitrogen (from hydrazone) and phenolic hydroxy group
possessing high affinity to transition metals could
Recognition and determination of biologically important
transition metals such as zinc is one of the major task of
analytical and supramolecular chemistry. Zinc, or more
precisely its divalent cation (Zn(II)) is the second most
abundant transition metal and essential trace element in
the living systems, for example the total amount of zinc in
the adult body equals to 2–3 g (1, 2). Zn(II) participates in a
number of biochemical and biological processes e.g.,
apoptosis, regulation of gene expression, neural signal
transmission and many others. Zn(II) ion is also known
as a cofactor of more than 300 proteins such as enzymes
and DNA regulation factors (3). It is proved that zinc
deficiency can lead to a number of serious pathological
states such as retarded growth in children, brain disorders
and high blood cholesterol. Moreover, neurodegenerative
disorders such as Alzheimer’s disease, epilepsy, ischemic
stroke, and infantile diarrhoea are closely related to the
imbalance in Zn(II) metabolism (4).
CONTACT Milan Jakubek
jakubek.milan@seznam.cz; VladimírKrálvladimir.kral@lf1.cuni.cz
First Faculty of Medicine, Charles University, Průmyslová
595, Vestec 252 50, Czech Republic
© 2018 Informa UK Limited, trading as Taylor & Francis Group

2
M. JAKUBEK ET AL.
provide promising way for the preparation of novel
type of synthetic receptors for the determination of
biological important metal ions such as Zn(II). It inspire
us to prepare and evaluate a new benzoisothiazole
receptor for the recognition and determination of Zn
(II) ions in the aqueous environment. Because zinc com-
plexes are perspective agents for the specific targeting
and recognition of nucleic acids (21), interaction of
synthetic receptor and its Zn(II) complexes with DNA
and RNA was also observed in this study.
was obtained in the yield of 240 mg (92%) as yellowish
solid.
1H NMR (DMSO-d6): δ 7.15 (7.18) (d, J = 9.1 Hz, 1H);
7.90 (m, 2H); 8.08 (m, 1H); 8.24 (m, 2H); 8.67 (8.59)
(d, J = 2.9 Hz, 1H); 8.89 (8.63) (s, 1H); 12.11 (bs, 1H);
12.75 (bs, 1H) ppm. 13C NMR (DMSO-d6): δ 117.22
(117.03); 119.66 (120.24); 121.71 (122.34); 122.94;
123.34; 126.59; 127.64 (127.39); 133.37; 133.92 (134.24);
140.01 (140.06); 141.73 (143.24); 147.38 (144.88); 156.05
(158.82); 162.77 (162.34) ppm. . ESI-MS (m/z): 347 [M + H]
+ . Elem. Anal. Calcd. for C14H10N4O5S: C, 48.55; H, 2.91;
N, 16.18. Found: C, 48.52; H, 2.90; N, 16.16.
2. Experimental section
2.1. Materials and method
2.3. Spectroscopic study of interaction of synthetic
receptor 1 with metal ions
All chemicals, solvents and nucleic acid were purchased
from Sigma–Aldrich (Czech Republic) and were used with-
out further purification. Product number of used DNA (from
salmon sperm) and RNA (from Torula utilis) were 31,149 and
83,850, respectively. UV–Vis absorption spectra were
recorded using Varian Cary 400 SCAN UV–Vis
Spectrophotometer (Varian, USA) where reference spec-
trum of a plain solvent was subtracted from all spectra of
real samples. The NMR spectra were obtained with a Bruker
Avance III 500 MHz (500 MHz for 1H and 125 MHz for 13C)
(Bruker, Germany) at 25 °C in DMSO-d6. The chemical shifts
(δ) are presented in ppm (relative to TMS = 0.000 ppm) and
the coupling constants (J) in Hz. Mass spectra were mea-
sured with a 3200 Q TRAP (AB Sciex, Canada) mass spectro-
meter fitted with an electrospray ion source. The analyte
dissolved in methanol was introduced directly into the ESI
source via a PEEK capillary at a flow rate of 10 μL/min.
Nitrogen was used as a nebulizer gas. The operating con-
ditions for the mass spectrometer were set as follows: ion-
spray voltage 5.5 kV; curtain gas 10, ion source gas(1) 18,
and ion source gas(2) 0 psig; ion source temperature ambi-
ent; declustering potential 60 V, entrance potential 10 V.
For UV-Vis ‘on-off’ study, 35 mg of synthetic receptor
(SR) 1 was dissolved in DMSO to make concentration of
0.01 M in a 10 mL volumetric flask. 1 mL of the solution
of SR 1 was taken into a 1000 mL volumetric flask, and
water was added to the total volume of 1000 mL in a
volumetric flask. Final concentration of the SR 1 in the
stock solution was 10 μM.
Calculated amounts of the metal salts (nitrates) were
dissolved in water/DMSO, 99:1, ν/ν, or above solution of
SR 1 in a 100 mL volumetric flask to make final con-
centration of the metal cation 10 μM.
UV-Vis spectra of the studied SR 1 were measured in
the presence and absence of the used cations. Data were
collected in the range 220–900 nm with 1-nm data spa-
cing in 1-cm quartz cell at scan rate 600 nm/min.
2.3.1. Determination of conditional binding
constants and complex stoichiometry of SR 1 with zn
(ii) ions
The association of SR 1 with Zn(II) ions was studied using
UV-Vis spectroscopy in aqueous solution (water/DMSO,
99:1, ν/ν). Because the solvent always significantly affects
the binding constants, all titrations were performed at
the same environment and the ratio of DMSO to water
was hold constant. Conditional constants (Ks) were cal-
culated from the absorbance changes ΔA of SR 1 at the
spectral maximum of their complexes with Zn(II) by non-
linear regression analysis with the Letagrop Spefo 2005
software. The computational model was described and
discussed in detail elsewhere (23). To express of error of
Ks was used standard deviation between measured and
calculated absorption intensity (based on the deter-
mined K). Their values was defined as twice the values
of these standard deviations.
2.2. Synthesis and characterisation of receptor 1
3-Hydrazinylbenzoisothiazole-1,1-dioxide (22) (138 mg;
0.7 mmol) and 2-hydroxy-5-nitrobenzaldehyde (167 mg;
1 mmol) were mixed in isopropanol (25 mL) and acetic
acid (1 mL) was added. Reaction mixture was then stirred
at 75 °C for 2 days. Then volatile compounds were
evaporated under reduced pressure and residue was
suspended in diethyl ether/petroleum ether mixture
(1:1 v/v; 30 mL). Solid material was filtered, washed
with additional portions of diethyl ether/petroleum
ether mixture (1:1 v/v; 60 mL) and dried at 50 °C under
vacuum. 2-{[2-(1,1-dioxidobenzoisothiazol-3-yl)hydraziny
lidene]methyl}V-4-nitrophenol (synthetic receptor 1)
The concentration of SR 1 was 10 μM. The concentra-
tions of Zn(II) varied in the range of 0–0.5 mM. UV-Vis

SUPRAMOLECULAR CHEMISTRY
3
spectra were measured from 220 to 900 nm with 1-nm
data spacing in 1-cm quartz cell at scan rate 600 nm/min.
their complexes with DNA, or RNA by non-linear regres-
sion with the Letagrop Spefo 2005 software. To express
of error of Ks was used standard deviation between
measured and calculated absorption intensity (based on
the determined K). Their values was defined as twice the
values of these standard deviations.
2.3.2. Determination of detection limit of SR 1 for zn
(ii) ions
The detection limit was determined from the titration
data (24, 25) in aqueous solution (water/DMSO, 99:1, ν/ν).
The values of the absorbance of SR 1 at 385 nm (UV
maximum of its zinc complexes) measured at various
concentrations of Zn (II) were normalized taking into
account the original absorbance at the absence of Zn
(II) in the solution versus the final maximal absorbance
(corresponding to the final addition of Zn(II)). A linear
regression curve was then fitted to the normalized
absorbance. The detection limits were calculated using
the following equation: LOD = D/K, where D is the
absolute value of the above curve for a zero concentra-
tion of Zn(II) and K is the slope of the dependence of the
normalised absorbance ((A − Amin)/(Amax − Amin)) vs. Zn
(II) concentration.
3. Result and discussion
3.1. Chemistry
SR 1 was prepared by reaction of 3-hydrazinylbenzoi-
sothiazole-1,1-dioxide (22) with excess of 2-hydroxy-5-
nitrobenzaldehyde in isopropanol in the presence of acetic
acid at 75 °C for 48 h in the yield of 99 % (Scheme 1).
3.1.1. Prototropic tautomerism
Heterocyclic hydrazones showed in some cases proto-
tropic tautomerism – equilibrium between amino form
(acidic proton is on the hydrazine nitrogen) and imino
form (acidic proton is on the heterocyclic nitrogen)
(Scheme 2). (22, 26) Prototropic tautomerism leads to
two sets of signals in 1H and 13C NMR spectra. The ratio
of tautomers is dependent on the pH and solvent; in
the case of SR 1 in DMSO-d6, the ratio of tautomers
calculated from the signals of the CH = N protons was
7:1. Ratio of tautomers was not significantly changed
after addition of various amount of D2O into DMSO-d6
solution. Based on it, we can expected, than initial
tautomer ratio in the water system (e.g. water/DMSO,
99:1, ν/ν), which was used for is approximately 7:1.
2.3.3. Study of interaction, determination of
conditional binding constants and complex
stoichiometry of synthetic receptor SR 1 and zinc
complex of SR 1 with nucleic acids
1 mL DMSO solution of SR 1 (0.01M) and 1ml water
solution of Zn(II) ions (0.01 M) were stirring for 15 minutes
together. Subsequently, 0.2 mL of the above prepared
solution of zinc complex of SR 1 (Zn-SR 1) (0.005 M) was
taken into a 100 mL volumetric flask, and 1mM HEPES
buffer with calculated amount of DNA, or RNA adjusted
on pH 7.34 ad was added to the total volume of 100 mL
in a volumetric flask. Solution of alone SR 1 was prepared
in the same way, instead of the aqueous solution of zinc
ions was used distilled water.
3.2. Uv-vis study of interaction of SR 1 with
transition metals
Because the DNA and RNA polymer chains have
various lengths, the Ks values of SR 1 and Zn-SR 1
with DNA and RNA were calculated using the DNA
and RNA concentration as defined by the concentration
of each repeated base pair and base, respectively. Final
concentration of SR 1 and Zn-SR 1 in the stock solution
was 10 μM. The concentrations of DNA and RNA varied
in the range of 0–0.1 mM. UV-Vis spectra were mea-
sured from 220 to 900 nm with 1-nm data spacing in 1-
cm quartz cell at scan rate 300 nm/min.
The association of the SR 1 and Zn-SR 1 with DNA and
RNA was studied using UV-Vis spectroscopy in 1mM
HEPES buffer (water/DMSO, 99:1, v/v), pH = 7.4. Because
the solvent always significantly affects the binding con-
stants, all titrations were performed at the same environ-
ment and the ratio of DMSO to water was hold constant.
Ks were calculated from the absorbance changes ΔA of
SR 1, or Zn-SR 1 with DNA, or RNA using the maximum of
Selectivity of the synthetic receptor for the recognition of
Zn(II) ion was studied by UV-Vis absorption spectroscopy.
This study was conducted in aqueous environment
Scheme 1. Preparation of SR 1.
Scheme 2. Prototropic tautomerism of SR 1.

4
M. JAKUBEK ET AL.
(water/DMSO, 99:1, ν/ν) at 10 μM concentration of both,
SR 1 and appropriate metal cation. SR 1 exhibited an
absorption peak at 271 nm. Upon the addition of equi-
molar amount of Zn(II) into the solution of SR 1 a signifi-
cant change of the absorption such as appearance of new
absorption peaks (λmax = 322 and 385 nm) was observed
(Figure 1). On the contrary, upon the addition of the other
metal ions such as Co(II), Cu(II), Fe(III), Ni(II), Cd(II) Pb(II), Cr
(III), Hg(II) Al(III), no or only slight spectra change was
observed. It indicated, that SR 1 prefer polarizable metal
ions such as Zn(II). Fact, than was not observed interaction
with Cu(II), which displayed similar properties with Zn(II)
such as charge, average and polarizability could be
explained geometry of created complex. It well known,
that ligands with ability to form complex with tetrahedral
geometry prefers Zn(II) ions other ions even Cu(II). (27)
In order to determine the applicability of SR 1 for the
determination of Zn(II) ions, the titration experiment was
performed (Figure 2). Detailed titration curves are showed
in Figure 2(c-d). In the presence of the added Zn(II) ions two
new absorption peaks (λmax = 322 and 385 nm) were
observed. As the concentration of Zn(II) ion gradually
increased the absorbance at the original spectral maximum
at 271 nm and at the two new maxima strongly increased
up to the concentration equal to 0.5 equivalents. Then the
further additions of Zn(II) ions lead to the slow increase of
the absorbance. Specifically, in the presence of 0.5 equiva-
lent of Zn(II) ions the absorbance at 385 nm rised more
than twice (from 0.05 to 0.12) with respect to the value at
the absence of Zn (II). The highest value of absorbance
(0.18) was observed when 296 Zn(II) equivalents were
added into the studied solution. Ks of SR 1 complex with
zinc (II) ion were calculated by Letagrop Spefo 2005. Their
value were 5.0x106 6 x105 and 1.3x1012 1.7x1011 for
complex 1:1 and 1:2 (Zn(II) ions: receptor), respectively.
3.3. Determination of the detection limit and
linear range of synthetic receptor 1 for zn(ii)
The detection limit of SR 1 for Zn(II) was determined
utilizing a plot of normalized absorbance versus the
concentration of the Zn(II) present in the solution (24,
Figure 1. (Colour online) UV-Vis spectra (a) and absorbance (b) at 385 nm of SR 1 (10 μM) with respect to the tested metal ions (10
μM) in aqueous medium (water/DMSO, 99:1, v/v).
Figure 2. (Colour online) UV-Vis spectra of SR 1 in the presence of zinc (II) ions (a) and titration curves (b, c and d) for SR 1 (10 μM),
dependence of the complex absorbance at 385 nm on Zn(II) concentration in aqueous medium (water/DMSO, 99:1, v/v).

SUPRAMOLECULAR CHEMISTRY
5
Figure 3. (Colour online) Limit of detection (a) and linear range (b) of SR 1 (10 μM) at 385 nm for Zn(II) in aqueous medium (water/
DMSO, 99:1, v/v).
25). As shown in Figure 3, a linear relationship between
the absorption intensity of studied SR 1 in solution and
the Zn(II) concentration was obtained. It was found that
the prepared SR 1 displayed very low limit of detection
0.15 μM. Linear range 0–4.5 μM implies its good poten-
tial for the determination of biologically relevant con-
centrations of Zn(II) ions. Average Zn(II) level found in
the brain tissue is between 0.1–0.5 mM (4). Thus, we
demonstrated that SR 1 is highly sensitive to Zn(II) and
it can be utilized to measure Zn(II) level in various
analytical and bioanalytical applications.
1). Scheme 3 proposed the binding interaction of SR 1
with Zn(II) ion. These results indicate the effective
Table 1. Various receptors described for the determination of
Zn(II) ions.
LOD
[μM]
Medium
(solvent ratio)
Receptor
Ref.
(8)
0.198 Acetonitrole/Tris–
HCl buffer
(9:1, v/v)
The detection limit of the prepared synthetic recep-
tor is comparable to other synthetic receptors for Zn(II)
(Table 1). As can be seen, the values of the detection
limits vary from 0.5 μM to 10 μM. It is well known that
one of the main disadvantages of synthetic receptors
stem in their limited usability in aqueous medium and
the presence of a significant amount of organic co-
solvent is necessary (Table 1). Organic additives sup-
press aggregation of the receptor and at the same time
they improve the detection limits.
1.2
Phosphate buffer/
Acetonitrile
(3:1, v/v)
(9)
1.56 Acetonitrile/HEPES
(10)
(11)
buffer
(9:1, v/v)
10.9 DMF/Bis-Tris buffer
(1:1, v/v)
0.6
3.7
Bis-Tris buffer/
DMSO
(99:1, v/v)
(12)
(13)
1
3.4. Study of the interaction mode using H NMR
1
The H NMR spectra of SR 1 in the absence and pre-
sence of 1 equivalent of Zn(II) ions (as its nitrate salt)
are shown in Figure 4. The results showed that the
signals were shifted upon the addition of Zn(II) ions
and the proton signals of the aromatic regions broa-
dened and overlapped. The most significant changes
upon the addition of Zn(II) ions occurred for the imine
proton: δ 8.89 ppm was shifted downfield to δ 8.76
ppm (Figure 4). Similarly was observed, that signals
arising from the other aromatic protons shift downfield
by δ 0.05–0.15, except for the proton in the hydroxy
group, which disappeared when the Zn(II) was com-
plexed by SR 1. This results implied, that two N atom
and one O atoms can participate on the complexation
of Zn(II) by SR 1. On this base, we proposed that Zn(II)
ion is bonded by phenolic oxygen, enamine nitrogen
and heterocyclic nitrogen (O-N-N binding system od SR
HEPES buffer/
Acetonitrile
(3:2, v/v)
9.87 DMSO/HEPES
buffer
(14)
(4:1, v/v)
(Continued)

6
M. JAKUBEK ET AL.
Table 1. (Continued).
390 nm raised approximately three times with relatively
to the absorption in the absence of DNA in the system
(from 0.11 to 0.28) (Figure 5). The above data are con-
sistent with the expected binding of Zn-SR 1 to the
DNA. On the other hand alternatively explanation
observed phenomena could be based on the dissocia-
tion of Zn-SR 1 in the presence DNA and binding
liberated SR 1 to DNA.
Therefore confirmation of tested hypotheses, inter-
action of alone of SR 1 with DNA was also studied
(Figure 6). After DNA addition SR 1 displayed also
complex formation coupled with a significant improve-
ment absorption (λmax = 364 nm). Hover its position of
maximum differed strongly from the maximum position
(λmax = 385 nm) found for the complex of Zn-SR 1 with
DNA. Differences in the shape and position of spectral
peaks of SR 1 and Zn-SR 1 in the presence of nucleic
acids indicated, that both of them can form complexes
with DNA.
LOD
[μM]
Medium
(solvent ratio)
Receptor
Ref.
(15)
1
Acetonitrile/Water
(4:1, v/v)
5.81 Methanol/Water
(4:1, v/v)
(16)
(17)
1.11 Acetonitrile
0.15 Water/DMSO
(99:1, v/v)
This
work
binding of Zn(II) ions by SR 1. Fourth ligand necessary
for formation of tetrahedral complex is probably nitrate
anion, or H2O from used salt (Zn(NO3)2.12H2O).
The interaction of SR 1 and Zn-SR 1 with RNA dis-
played similar pattern as the one obtained for the inter-
action with DNA (Figures 7 and 8). Positions of their
absorption maxima were similar as in the previous case.
Nevertheless the extent of the increase in absorbance
observed for titration with RNA was significantly lower
than in the case of DNA. On the other hand, values of Ks
3.5 Interaction of zn-SR 1 and SR 1 with nucleic
acids
Zn-SR 1 was generated in situ in the used medium. Its
interaction with nucleic acid (DNA and RNA) was stu-
died by absorption spectroscopy. As the concentration
of DNA gradually increased absorbance of the original
peak (λmax = 385 nm) in UV spectrum significantly
increased and it displayed moderate red shift to
390 nm up to 2 equivalents. For example, in the pre-
sence of 2 equivalents of DNA the absorbance at
Scheme 3. Proposed binding interaction of SR 1 and Zn(II)
yielded 1:1 complex
1
Figure 4. (Colour online) H NMR spectra of SR 1 upon addition of Zn(II) in DMSO-d6.

SUPRAMOLECULAR CHEMISTRY
7
Figure 5. (Colour online) UV-Vis spectra of Zn-SR 1 in the presence of DNA (a) and titration curve (b,) for Zn-SR 1 (10 μM)
dependence of the complex absorbance at 390 nm on DNA concentration in 1mM HEPES buffer (water/DMSO, 99:1, v/v), pH = 7.34.
Figure 6. (Colour online) UV-Vis spectra of SR 1 in the presence of DNA (a) and titration curve (b,) for SR 1 (10 μM) dependence of
the complex absorbance at 364 nm on DNA concentration in 1mM HEPES buffer (water/DMSO, 99:1, v/v), pH = 7.34.
Figure 7. (Colour online) UV-Vis spectra of Zn-SR 1in the presence of RNA (a) and titration curve (b,) for Zn-SR 1 (10 μM)
dependence of the complex absorbance at 390 nm on RNA concentration in 1mM HEPES buffer (water/DMSO, 99:1, v/v), pH = 7.34.
Figure 8. (Colour online) UV-Vis spectra of SR 1 in the presence of RNA (a) and titration curve (b,) for SR 1 (10 μM) dependence of
the complex absorbance at 364 nm on RNA concentration in 1mM HEPES buffer (water/DMSO, 99:1, v/v), pH = 7.34.
of SR 1 and Zn-SR 1 with DNA were not significantly
higher than for their complexes with RNA (you seen in
Table 2), stoichiometry of observed complexes was 1:1.
Alone SR 1 displayed significantly higher affinity for
the RNA against DNA, while Zn-SR 1 don’t show
significantly RNA preference. It is well known, that
DNA have twice the number of binding sites (e.g.
bases) than RNA. Based on this, one can expect that
these receptors should be higher preference for the
DNA. On the other hand, unlike DNA, RNA bases are

8
M. JAKUBEK ET AL.
Table 2. The Ks of Zn-SR 1 and SR 1 with DNA and RNA.
Competitiveness [CZ.2.16/3.1.00/21537]; Ministry of Education,
Youth and Sports of the Czech Republic [BIOCEV-FAR, CZ.1.05/
1.1.00/02.0109, LM201564, LQ1604] and National Programme of
Sustainability [MSMT-43760/2015]; Charles University in Prague
[PRVOUK P24/LF1/3, UNCE 204011/2012]; Ministry of Agriculture
of Czech Republic (QJ1610515)
Nucleic acid
DNA
RNA
Receptor
Zn-SR 1
SR 1
Log Ks
5.7 0.23
4.9 0.17
Log Ks
5.9 0.28
6.1 0.15
aStoichiometry of complexes was 1:1.
not bound by complementary bases via hydrogen bond
and therefore they can be more accessible for interac-
tion. Fact that both tested receptors prefers RNA sug-
gests, they interact with nucleobases via hydrogen
bond, or other non-covalent interaction. It is implied,
that not only SR 1, but also metal complexes such as
Zn-SR 1 can represent perspective structure motif for
the recognition and targeting nucleic acids.
ORCID
Pavel Martásek
http://orcid.org/0000-0001-6165-4444
References
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(3) Palmgren, M.G.; Clemens, S.; Williams, L.E.; Kraemer, U.;
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(4) Bush, A.I.;. Metals and Neuroscience. Curr. Opin. Chem.
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4. Conclusions
In the present work the novel type of zinc receptor
based on benzoisothiazole-1,1-dioxide structure motif
was synthesized and studied. Its chemical structure was
characterised by NMR and MS. Its binding ability was
evaluated with absorption spectroscopy. The prepared
SR 1 exhibited selective spectroscopic response for Zn(II)
ion in aqueous medium with low detection limit of 0.15
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Acknowledgments
This work was supported by the Ministry of Education, Youth and
Sports of the Czech Republic within the National Sustainability
Program II [Project BIOCEV-FAR, LQ1604] and by the project
‘‘BIOCEV’’ [CZ.1.05/1.1.00/02.0109]; the Technology Agency of
the Czech Republic [project TE01020028]; Charles University in
Prague [UNCE 204011/2012 and PRVOUK P24/LF1/3]. This work
was also supported by the “Operational Programme Prague –
Competitiveness” (CZ.2.16/3.1.00/21537) and the “National
Programme of Sustainability I” - NPU I (LO1601 - No.: MSMT-
43760/2015). Besides, we also thank for the financial support of
this work the Ministry of Education, Youth and Sports of the Czech
Republic grant no. LM201564 (EATRIS-CZ). This work was also
supported by Ministry of Agriculture of Czech republic
[QJ1610515] and Ministry of Industry and Trade [FV20572].
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Disclosure statement
No potential conflict of interest was reported by the authors.
(10) Choi, Y.W.; Park, G.J.; Na, Y.J.; Jo, H.Y.; Lee, S.A.; You, G.R.;
Kim, C. A Single Schiff Base Molecule for Recognizing
Multiple Metal Ions: A Fluorescence Sensor for Zn(II)
and Al(III) and Colorimetric Sensor for Fe(II) and Fe(III).
Funding
This work was supported by the Technology Agency of the Czech
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Republic [project TE01020028]; Operational Programme Prague –
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