Phenolic oxime based receptors for selective detection of fluoride

Article abstract of DOI:10.1039/c5ra15460j

The possibilities to employ phenol and oxime functionalities as the fluoride recognition motif are investigated. In this regard, two new phenolic oximes H1 and H2 were prepared where the two units are linked via different aliphatic spacers. Among them, H1 exhibits intense and instantaneous colour change upon addition of fluoride ion which is clearly discernible by the "naked eye". Optical, ¹H NMR and CV analysis established that H1 is a highly selective receptor for fluoride ion as compared to other anions tested during this investigation.

Full text of DOI:10.1039/c5ra15460j

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ARTICLE TYPE
Phenolic oxime based receptors for selective detection of fluoride
a
Suchibrata Borah, Bhrigu Phukan Das, Gayatri Konwar, Sanjeev Pran Mahanta* and Nayanmoni
Gogoi*
Received (in XXX, XXX) XthXXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
The possibilities to employ phenol and oxime functionalities as the fluoride recognition motif are
investigated. In this regard, two new phenolic oximes H1 and H2 were prepared where the two units are
linked via different aliphatic spacers. Among them, H1 exhibits intense and instantaneous colour change
1
upon addition of fluoride ion which is clearly discernible by “naked eye”. Optical, H NMR and CV
1
0
analysis establishes that H1 is a highly selective receptor for fluoride ion as compared to other anions
tested during this investigation.
Introduction
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transportation limits their utility. Thus, development of a simple,
economical, highly selective, sensitive and rapid fluoride
detection method for practical purpose is worthwhile. In this
regard, colorimetric and fluorometric sensors for fluoride
recognition with high selectivity and sensitivity have received
considerable attention. A plethora of abiotic receptors exploiting
the diversity of nonꢀcovalent interactions which feature cationic
sites, Lewis acidic sites, electronꢀdeficient πꢀsystems and Hꢀbond
donor motifs have been designed and their anion binding
Anions are ubiquitous in nature and many of them play important
roles in biology, medicine, agriculture, catalysis and
environmental sciences. Therefore the selective recognition,
sensing and extraction of anions has evolved as a fevered area of
1
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3
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0
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1
research during the last decade. In this context, the rational
design and synthesis of new abiotic receptor molecules which can
bind anions of interest with high affinity and selectivity has
remained one the most pressing challenges in supramolecular
2
chemistry. Among various anions, the selective recognition and
5
ꢀ
behaviour explored. Conventional hydrogen bonded F binding
receptors rely on either adjacent reporter (i.e. chromogenic and
fluorogenic) units or deprotonation followed by electron
delocalization to display a colorimetric response. Therefore, most
sensing of fluoride ion has been the subject of intensive research
due to its relevance in environment and health sectors. Fluoride
3
has many industrial applications and used as an essential additive
in toothpaste to prevent corrosion of teeth by acids. Fluoride is
also used as an ingredient in drugs to treat the brittleꢀbone disease
called Osteoporosis. The main source of fluoride in water is
basically geogenic. United States Environmental Protection
Agency (EPA) puts the maximum contamination level goal
ꢀ
of the receptors cannot differentiate F from other anions with
same or more basicity.
Fluoride exhibits unique physicoꢀchemical properties due to its
smaller size and high electronegativity. Moreover, due to its high
hydration enthalpy, fluoride is not willing to bind with (or
recognize) other molecules in presence of water. Therefore the
3
(MCLG) for fluoride in drinking water as 4 ppm. 0.7ꢀ1.2 ppm
level of fluoride in drinking water is sufficient to maintain public
health dental benefits of caries prevention while also minimizing
the incidence of enamel fluorosis. Excessive intake of fluoride
has many severe health implications viz. fluorosis and
ꢀ
receptor has to compete with water for fluoride i.e. with OꢀH…F
ꢀ
6
interaction of F and water. Hence the design of receptors
capable of binding fluoride ion efficiently and selectively in
water i.e. for realꢀlife applications is consequently a meaningful,
3
osteofluorosis. Thus accurate determination of the amount of
5
however challenging task. In order to achieve enhanced
fluoride in drinking water and living organs is important.
Generally, ion selective electrodes, ion chromatography, Willardꢀ
Winter methods are used for quantitative detection of fluoride ion
but the very high cost and difficulty in handling as well as
selectivity towards fluoride, fine tuning of interaction sites are
required, which in turn needs appropriate functionalization, such
that the complementarity of interacting sites, size and shape
between the receptor and the guest has to be achieved. It is
envisaged that fine tuning of the acidity of the hydrogen bond
donor sites is crucial for designing Hꢀbonding neutral receptors
7
4
0
Department of Chemical Sciences, Tezpur University, Napaam
Sonitpur 784028, Assam, India.
Email: samahan@tezu.ernet.in, ngogoi@tezu.ernet.in.
8
capable of binding fluoride ion in aqueous environment. In
principle, more acidic the binding sites, the probability of the
receptor to bind fluoride in aqueous environment would be
higher. Therefore, it is presumed that incorporation of hydroxyl
group in a flexible scaffold suitable for fluoride size may be a
†
Electronic supplementary information (ESI) available:
4
5
Including additional spectroscopic data and crystal structure data
CCDC 1406653. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/b000000x
This journal is © The Royal Society of Chemistry [year]
[journal], [year], [vol], 00–00 |1

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practical strategy for fluoride discrimination in aqueous medium.
In addition, the use of highly acidic hydrogen bond donor sites
may favour deprotonation which can subsequently alter the
electronic structure of the receptor and consequently a remarkable
change in colour of the solution with a large bathochromic shift is
expected which provides naked eye visualization of the
recognition event. Towards this, a number of receptors with
hydroxyl group as binding motif were reported and their anion
5
9
binding properties were bstudied.
Scheme 2 Synthesis of receptor H2: (a) CH CH OH, RT, 4h (b)
3
2
CH CH OH, reflux, overnight.
3
2
4
4
5
0
5
0
10
15
20
Figure 1 Structure of receptor H1 and H2.
Both the compounds were characterized by using standard
1
13
spectroscopic techniques such as
H
NMR,
C NMR
Herein we have designed and reported the synthesis and anion
binding properties of a new class of receptor, H (H1 and H2)
containing oxime and phenol hydroxyl groups as the Hꢀ bonding
recognition unit (Figure 1). In case of H1 the recognition units
are separated by the conjugated aliphatic spacer containing imine
moiety while in H2 conjugation breaks due to the presence of the
amide moiety. Phenolic and oxime hydroxyl groups have
different acidities, and therefore have different Hꢀbonding
spectroscopy and elemental analysis. Further, solid state
structures of compound H1 was unequivocally elucidated by
single crystal Xꢀray diffraction method with a crystal grown by
1
slow evaporation of ethanol solution. H NMR spectrum of H1 in
1
DMSOꢀd shows two hydroxyl H peaks at 11.92 and 11.28 ppm
6
which clearly reveals the highly acidic nature of the hydroxyl
protons. Further, it is observed that the compound isomerizes on
1
keeping the sample for longer time as DMSO solution. H NMR
1
0
affinities. In addition, these two OH moieties have higher
acidities compared to water. Therefore, it is envisaged that these
two hydroxyl moieties can compete with water to bind fluoride
spectra of the aforementioned solution shows the emergence of
new peaks slightly downfield to the prevailing hydroxyl peaks
and this can probably be attributed to the emergence of new
isomers in the solution (Figure 2).
1
0
ion in aqueous medium.
55
Figure
2
Change in NMR spectra of H1 in DMSOꢀd6 while
25
3 3 2
Scheme 1 Synthesis of H1: (a) CH OH, RT, 2h (b) CH CH OH, reflux,
1
isomerization. (a) Hꢀ NMR spectraꢀ bottom: pure isomer, top: isomeric
overnight
13
mixture; (b) Cꢀ NMR spectraꢀ bottom: pure isomer, top: isomeric
mixture.
Results and discussion
60
This study infers the presence of a dynamic equilibrium between
two conformational isomers of compound H1 in DMSO (Scheme
3) and the integration of the corresponding signal established the
ratio of the two isomer as 2:1 showing 30 % isomeric conversion.
Synthesis and characterization
Receptor H1 was conveniently synthesized by a twoꢀstep
reaction scheme from 2,3ꢀbutanedionemonoxime. The synthesis
30
involves the preparation of monoximehydrazone from 2,3ꢀ 65 UVꢀvisible spectra of H1 in DMSO reveal two absorption
butanedione monoxime followed by its Schiff base condensation
reaction with salicylaldehyde (Scheme 1) which yield compound
H1 as yellow crystalline solid. Receptor H2 was synthesised
maxima (λmax) at 294 and 338 nm. Single crystal Xꢀray
diffraction analysis reveals the transꢀorientation of the oxime
double bond w.r.t. the NꢀN single bond in the solid state (Figure
2). Solid state packing pattern reveals the occurrence of
11
35
conveniently from ethylꢀ2ꢀhydroxybenzoate by following scheme
1
2
2
as a light yellow colour solid.
2
|Journal Name, [year], [vol], 00–00
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ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
various anions (F , Cl , Br , I , CN , CH COO , H PO , HSO ,
3
2
4
4
ꢀ
ClO ) as their tetrabutylammonium salts. Further, the
4
45
mechanistic study of binding was also performed with the help of
H NMR spectroscopy in DMSOꢀd6.
1
Scheme 3 Plausible isomeric structure of H1 in DMSO.
5
5
6
0
5
0
intramolecular OꢀH….N hydrogen bond (with 2.597Å distance,
˂OꢀH..N=147.7˚) between phenolic OH and hydrazine nitrogen
atom and intermolecular OꢀH….N hydrogen bond (with 2.855 Å
distance, ˂OꢀH..N=175.8˚) between oxime OH and oxime N of a
nearby molecule (Figure 4, inset). Further, careful analysis of the
packing pattern reveals the presence of the herringbone packing
mode which is facilitated by slip stacked πꢀπ stacking interaction
between the phenyl rings (Figure 4). Further, Hirshfeld surface
5
Figure 5 Change in colour of H1 (20 ꢁM) in dry DMSO after the addition
of 10 equivalents of tetrabutylammonium salt of anions.
1
0
13
It is presumed that the two preorganized OꢀH Hꢀbond donor
moiety interact with anionic guest which are principally Hꢀbond
acceptors and exhibit certain change in spectroscopic properties
upon interaction with anions which make visualization of the
anion binding events meaningful. It is observed that the solution
changes its colour from colourless to dark yellow upon addition
of fluoride to H1 solution in DMSO which can be easily detected
by naked eye whereas the change with cyanide was less
prominent. However, no colour change was observed upon
addition of other anions (Figure 5). However, receptor H2 does
not show any naked eye detectable colour change upon addition
of the tested anions.
analysis of the crystal structure also confirms the same (ESI).
15
6
5
20
Figure 3 ORTEP diagram of H1, with the displacement ellipsoid drawn
at the 35% probability level. Crystal data: C11H13N3O2, a = 19.7074
(7) Å, b = 4.4839(5) Å, c = 12.7541 (5) Å, α = γ = 90˚, β = 107.994˚ (2),
70
2
3
3
5
0
5
V = 1071.91 (8), T = 296 K, Monoclinic, Space group P2(1)/n, z = 4.
Colour code: red: O, blue: N, grey ellipsoid: C, grey sphere: H.
1
H NMR spectra of receptor H2 features three singlets at
1
1.29, 11.49 and 11.60 ppm which corresponds to the two
hydroxyl protons and the amide NH proton. This large down field
shift of the aforesaid protons indicates their highly acidic
character. However, unlike H1, H2 does not show any noticeable
conformational isomerisation in DMSOꢀd . Unfortunately, even
6
after repeated attempts we could not obtain any good quality
crystal to determine the solid state structure of H2.
Figure 6 Left: UVꢀVis absorption spectra of H1 in dry DMSO
(20 ꢁM) after addition of 10 equiv. of different anions in the form
of TBA salts. Right: Intensity of the new 445 nm peak after
addition of 10 equiv. of different anions in the form of TBA salts.
7
8
8
9
5
0
5
0
Figure 5 depicts the change in colour of receptor H1 upon
addition of 10 equivalents of the respective anions which clearly
reveals that the receptor shows highest optical change towards
fluoride ion, somewhat lesser extent toward cyanide ion and little
to none towards other anions. To verify the change in electronic
structure and selective fluoride binding, the changes in UVꢀVis
absorption of the receptors were recorded in dry DMSO (20 ꢁM
solution), after adding 10 equivalent of the respective
ꢀ
tetrabutylammonium salts. As depicted in figure 6, only F ion
ꢀ
and CN ion induces instantaneous bathochromic shift in the
Figure 4 Herringbone packing pattern of H in the solid state showing.
absorption maxima and all other anions did not induce any
Inset: Hꢀbonding structure in the solid state packing.
ꢀ
ꢀ
perceptible change in the UVꢀVis spectrum. In case of F and CN
ion, UVꢀVis study shows the emergence of a new peak at ~445
nm which could be the reason behind the observed colour. The
bar diagram clearly reveals that the intensity of the newly
emerged peak is maximum in case of fluoride (Figure 6). The
observed colour change might be due the alteration of the
4
0
Anion binding study
Preliminary solution phase anion binding studies were carried
out using UVꢀvisible spectroscopy in dimethyl sulfoxide with
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5
5
6
0
5
0
5
1
1
2
0
5
0
Figure 7 Change in colour of H2 (20 ꢁM) in dry DMSO after the addition
of 10 equivalents of tetrabutylammonium salt of anions.
Figure
9
CVs recorded in nꢀBu
4
NClO
4
/DMSO. Green: H1 with
-
TBAClO
4
as electrolyte; Pink: H1 with TBAF as electrolyte; Blue: H1.F
as electrolyte.
electronic environment of H1 as a result of charge transfer due to 65 with TBAClO
4
deprotonation upon fluoride binding. However, in case of
addition of TBAF led to two oxidations at Ep,a = 0.05 and 0.92
V while in the negative scan, two reduction peaks at Ep,c = ꢀ1.5
V and 0.12V were observed. This may be due to the oxidation of
both phenolic as well as oxime moiety in presence of fluoride ion.
To verify the contribution of fluoride ion in the change in
electrochemical behaviour of H1, we have recorded the CV with
TBAF as the supporting electrolyte which clearly shows a
different pattern compared to that of the CV recorded with
tetrabutylammonium perchlorate as electrolyte. This study clearly
reveals that upon addition of fluoride, the integrity of H1 has lost
which may be due to deprotonation of the hydroxyl groups and
subsequently led to a different electrochemical behaviour.
However, addition of fluoride to H2 does not affect its
electrochemical properties significantly as compared to H1 (ESI).
Furthermore, to examine the binding selectivity and sensitivity
of H1 in a complex environment of potentially competing anions,
receptor H2 the absorption spectra retain its identity even after
addition of large excess of anions (Figure 7). This clearly reveals
that the binding of anion to receptor H2 does not induce any
significant modification in the electronic structure of the receptor.
To verify the binding selectivity of receptor H2, we have studied
7
7
8
0
5
0
1
the interaction between receptor H2 and anions with H NMR
2
5
spectroscopy in DMSOꢀd . The study shows the disappearance of
6
1
the H NMR signal corresponding to the –OH proton after
ꢀ
ꢀ
addition of F and CN but other ions did not show any significant
change. However, it is observed that the amide protons did not
participate in the recognition event. This observation reveals that
like H1, H2 also shows selective binding towards F and CN
Figure 8).
ꢀ
ꢀ
3
0
(
1
Figure 8 A portion of H NMR spectra in DMSOꢀd
6
of (a) H2 (b) H2 in
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
35
presence of Cl , Br , I , CH
3
COO , H
2
PO
4
ꢀ
, HSO
4
, ClO
4
(c) H2 in
ꢀ
presence of CN (d) H2 in presence of F .
The fluoride recognition event of receptor H was further studied
with cyclic voltammetry in DMSO which provides evidence of an
anionꢀdependent electrochemical response with fluoride ions.
Analysis of the CV of H1 with TBAClO4 as supporting
electrolytes reveals a single oxidation at Ep,a = 0.92 V while on
the negative scan, two reduction peaks occurred at Ep,c = ꢀ0.48 V
and ꢀ0.98 V. The appearance of two cathodic peaks may be due
to the reduction of two phenol oxidation product i.e.
4
0
8
5
Figure 10 (a) Evolution of UVꢀVis spectra of H1 in DMSO upon gradual
addition of TBAF (b) Job’s plot of H1 vs. TBAF in DMSO (C) Benesiꢀ
Hildebrand plot of titration data of H1 vs. TBAF (d) UVꢀVis spectra:
Red: H1; Gray: H1 and TBA salts of other anions and Blue: addition of
TBAF in H1 combined with other anions.
45
14
orthoquinone to orthophenol and paraquinone to paraphenol.
However, CV of H1 does not provide any information regarding
the redox behaviour of the oxime moiety. Whereas
90
4
|Journal Name, [year], [vol], 00–00
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the screening is investigated in presence of other anions tested in
the solution. The experiment is performed by adding fluoride to a
with concomitant up field shift indicating Hꢀbonding interaction
between the two moiety (Figure S20ꢀS21, ESI). Further increase
solution containing receptor H1 along with other anions. 45 in anion concentration results in the disappearance of the OH
ꢀ
Interestingly, it is observed that only the presence of CN ion can
signal due to broadening, up field shift of the aromatic CꢀH
protons and concomitant splitting of the phenyl CH peaks into
multiple signals. Finally after addition of ~ 2 equiv. of TBAF the
ꢀ
5
interfere with the detection of F ion but to a very small extent,
while other anions did not show any remarkable interference with
the detection process (Figure 10d). In order to evaluate the
ꢀ
peak due to HF2 appears at ~ 16 ppm which clearly indicates the
binding affinity of receptor H1 towards fluoride, systematic 50 deprotonation of the hydroxyl proton. Also the up field shift of
spectrophotometric titration was carried out in DMSO with
varying concentration of fluoride ion, which indicated a strong
binding event, accompanied by gradual emergence of a new peak
at 445 nm. Job’s plot analysis shows the maximum at 0.5 which
the phenyl CH protons clearly indicates the increase in electron
density in the phenyl ring which again supports the deprotonation
of the acidic protons. Furthermore the H NMR titration
1
1
2
2
0
5
0
5
1
experiment in acetonitrileꢀd also reveals the same phenomena
3
dictates the formation of a 1:1 complex (Figure 10b). From the 55 with complete resolution of the phenyl CH peaks into four signals
titration data the association constant K for fluoride anion was
with equal intensity (Figure S22, ESI). This indicates that
deprotonation restricts the conformational dynamics of H1 and as
a result all the phenyl protons appear as chemically different
protons. It can be concluded that the restriction of conformational
dynamics may favour facile delocalization and hence favours
dissipation of the excess electron density via the conjugated
imine spacer leading to the observed colour change. For further
confirmation of the deprotonation process, we have recorded the
a
calculated by using Connor equation where the linear fitting is
1
5
achieved by following BenesiꢀHildebrand method. The
4
ꢀ1
calculated binding constant is found to be 2.17 × 10 M .
60
To check the versatility of our synthesized receptor H1 we
have checked the binding in aqueous medium. Although it is
observed that receptor H1 shows prominent colour change upon
TBAF in DMSOꢀwater mixture, unfortunately it fails to detect
fluoride ion when added as sodium fluoride.
1
H NMR spectra of H1 in presence of hydroxide ion which has
65 comparatively higher basicity than fluoride. Like fluoride,
addition of hydroxide ion to H1 solution results the change in
1
colour of the solution towards red and H NMR spectra reveals
the complete disappearance of the hydroxyl proton signals and a
significant up field shift of the aromatic CH signals (ESI). This
70
unequivocally concludes that H1 recognizes fluoride via
deprotonation of the hydroxyl proton atleast at higher
1
concentration of fluoride. As expected, the quantitative H NMR
titration study of receptor H2 with TBAF also shows broadening
and gradual downfield shift of the hydroxyl proton signal along
with concomitant up field shift of the phenyl CH proton and
75
ꢀ
emergence of the HF2 signal at ~ 16 ppm after addition of
approximately 2 equivalent of TBAF. However, as observed in
1
the anion screening experiment, H NMR titration
1
Figure 11 Selected portions of H NMR indicating changes in the
1
H NMR spectra of H1 (10 mM) upon gradual addition of TBAF
in DMSOꢀd : (a) Free H1 (b) H1+ 0.2 equiv. TBAF (c) H1+ 0.4
6
equiv. TBAF (d) H1+ 0.6 equiv. TBAF (e) H1+ 1.0 equiv. TBAF
(f) H1+ 1.5 equiv. TBAF (g) H1+ 2.0 equiv. TBAF (h) H1+ 3.0
equiv. TBAF.
3
3
4
0
5
0
1
Further the mode of binding was studied with the help of H
NMR spectroscopy titration in DMSOꢀd6. Addition of 0.2
equivalents of TBAF to H1 solution results a broad peak at ~ 12
ppm. However it is not clear whether the disappearance of the
1
peak at 11.28 ppm is due to deprotonation or due to the merging 80 Figure 12 Selected portions of H NMR indicating changes in the
1
of the two peaks at 11.98 and 11.28 ppm due to the formation of
H NMR spectra of H2 (10 mM) upon gradual addition of TBAF
in DMSOꢀd : (a) Free H2 (b) H2+ 0.2 equiv. TBAF (c) H2+ 0.4
equiv. TBAF (d) H2+ 0.6 equiv. TBAF (e) H2+ 1.0 equiv. TBAF
(f) H2+ 1.5 equiv. TBAF (g) H2+ 2.0 equiv. TBAF (h) H2+ 3.0
-
H1: F complex since aromatic CH signals does not indicate any
6
significant change in the electronic ring current upon fluoride
addition (Figure 11). However addition of another 0.2 equiv. of
TBAF results broadening and downfield shift of the OꢀH signal 85 equiv. TBAF.
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Experimental Section
Materials and methods
experiment also does not infer any involvement of the amide
protons in the recognition process. This indicates that in these
receptors binding is controlled by acidity of the Hꢀbond donors.
1
Melting points were recorded on a JSCW melting point
apparatus. Elemental analysis was done by using Perkin Elmer
PR 2400 series analyzer. Infrared spectra were recorded with a
Nicolet Impact Iꢀ410 FTꢀIR spectrometer as KBr diluted discs.
5
0
5
0
5
H NMR experiments finally concludes that the fluoride
6
6
7
7
8
0
5
0
5
0
recognition by receptor H involves interaction via OꢀH…Fꢀ
hydrogen bonding followed by deprotonation of both the phenolic
and oxime protons indicating the involvement of the two
hydroxyl protons in the recognition and a possible 1:2 recognition
event. However, UVꢀVis Job’s plot analysis reveals 1:1
complexation in contrast to the 1:2 binding evident from NMR
experiments. This surprising anomaly may be due to the
occurrence of two step recognition event where first step is the
binding of fluoride ions through Hꢀbond followed by
deprotonation of the hydroxyl protons. At low fluoride
concentration i.e. the concentration range (20 ꢁM) at which the
UVꢀVis Job’s experiment was performed, the first process may
control the event while at comparatively higher concentration of
fluoride (i.e. > 1mM) both the process may be functional. Further
the shift of the isobestic point during gradual addition of TBAF
also suggest the presence of more than one stoichiometric species
1
13
The H NMR spectra (400 MHz) and C NMR spectra (100
MHz) were recorded on a ‘JEOL’ NMR spectrophotometer in
1
1
2
2
DMSOꢀd at room temperature. In NMR spectra, chemical shifts
6
are reported in parts per million downfield of Me Si (TMS) as
4
internal standard. The diffraction data was obtained with a
Bruker Smart APEXꢀ II diffractometer with MoꢀKα rotating
anode generator, and Smart CCD detector. Structures were solved
and refined using SHELXLꢀ97 with anisotropic displacement
parameters for nonꢀH atoms. The hydrogen atoms on O and N
atoms were located from the Fourier map in all of the crystal
structures. All C–H atoms were fixed geometrically. Empirical
absorption correction was done using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm. A check
of the final CIF file using PLATONS3 did not show any missed
16
in solution indicating the presence of a complex process. We
1
symmetry. UVꢀvisible data were recorded with a Shimadzu
UV2450 spectrophotometer.
titration studies were carried out on a Bruker Avanceꢀ400 MHz
NMR spectrometer in acetonitrileꢀd . UVꢀvisible titrations were
have tried to determine the stoichiometry by
H NMR
1
H NMR spectroscopy based
experiments. But unfortunately due to the large broadening and
splitting of the concerned signals, the experiments did not give
any conclusive result.
3
carried
out
in
dimethylsulphoxide
solution.
All
tetrabutylammonium salts for NMR andUVꢀVis titration were
purchased from SigmaꢀAldrich and used as such. All anions
Conclusion
®
To summarize, we have synthesized a new class of receptor H
were used in the form of their tetrabutyl ammonium salts
with two competing hydroxyl binding domain for instantaneous 85 (fluoride as its trihydrate). The receptor solutions were titrated by
30
35
40
45
50
55
and selective detection of fluoride in organic as well as in
aqueous medium. This study infers that strategic modulation of
the aliphatic spacer led to a remarkable change in the reporting
property (i.e. optical, electrochemical etc.) of the hostꢀguest
adding known quantities of concentrated solution of the anions in
question. The anion solutions used to effect the titrations
contained the receptor at the same concentration as the receptor
solutions into which they were being titrated so as to nullify the
recognition event. H1 shows solvent induced isomerization which 90 dilution effect.
1
was unequivocally confirmed by H NMR. Anion binding
studies reveals that both H1 and H2 are selective towards fluoride
ion and among them H1 shows a sharp colour change.
1.1. Synthesis of H1
Competition experiments also confirms the fluoride induced color
1
A mixture of salicylaldehyde (122 mg, 1 mmol) and diacetyl
monoxime hydrazone (115 mg, 1 mmol) was taken in a round
bottom flask and dissolved in 50 mL ethanol. The solution was
refluxed for 4 h with continuous stirring. The resultant solution
was cooled to room temperature and filtered. The yellow
change in presence of other tested anions. H NMR titration
95
analysis concludes that fluoride recognition involves binding of
ꢀ
fluoride via OꢀH...F hydrogen bonding followed by
deprotonation. Finally, we have shown that the simple aromatic
hydroxyꢀaldoxime conjugates can act as a binding domain for
fluoride discrimination. Fluoride binding was found to act
through binding followed by deprotonation of the hydroxyl
protons which led to large bathochromic shift in the absorption
spectroscopy and as a consequence a naked eye optical readout
coloured filtrate was kept undisturbed in
a beaker for
1
1
1
00 crystallization at room temperature. Yellow block shaped crystals
were observed after 2 days at the bottom of the beaker. The
solvent was decanted and the solid was dried in air which yield
1
27 mg of H1 as light yellow solid.
(colourless to dark yellow) is observed. Electrochemical study
further demonstrates phenolic oximes as potential fluoride
binding motif for electrochemical fluoride sensor. Unfortunately
this receptor cannot recognize inorganic fluoride salts such as
metal fluorides in aqueous medium which is the main objective of
our research. This observation limits the utility of our receptor for
field application. Presently, further study is going on to modulate
the system in order to enhance its hostꢀfluoride response in
aqueous medium.
ꢀ
1
05 Yield: 127 mg, 58 %; m.p.:122ꢀ124 °C; FTꢀIR (νmax/cm ,KBr):
3
1
7
201(br), 3052(w), 1964(w), 1612(s), 1543(w), 1492(w),
359(m), 1267(m), 1202(m), 1147(m), 1011(m), 941(m), 796(w),
1
50(m), 702(m), 649(w); H NMR (DMSOꢀd , 400 MHz, δ in
6
ppm): 11.92 (s, 1H), 11.28 (s, 1H), 8.71 (s, 1H) 7.64 (d, J=7.32
10 Hz, 1H), 7.35 (t, J=7.76 Hz, 1H), 6.9 (m, 2H), 2.18 (s, 3H), 2.02
13
(
s, 3H). C NMR (DMSOꢀd , 100 MHz, δ in ppm): 162.16,
6
1
56.78, 155.15, 131.33, 120.33, 40.22, 40.02, 39.81, 11.70, 9.85
6
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1
1
5
1
64.60, 161.23, 159.25, 155.24, 133.55, 131.71, 120.07, 118.96, 50 Notes and references
16.94, 13.48, 9.89. Elemental analysis: Found: C, 59.93; H,
1
In Supramolecular Chemistry of anions, ed. A. Bianchi, E. Garciaꢀ
Epsána and K. BowmanꢀJames, WileyꢀVCH, New York, 1997; J. L.
Sessler, P. A. Gale and W.ꢀS. Cho, in Anion Receptor Chemistry,
RSC Publishing, Cambridge, UK, 2006.
.99; N, 15.10. Calc. for C H N O : C, 60.27; H, 5.98; N,
1
1
13
3
2
9.16%; UVꢀVis: λmax (DMSO)/ nm: 294, 338.
5
5
6
6
5
0
5
2
E. GarććıaꢀEspàna , P. Dίaz, J. M. Llinares and A. Bianchi Coord.
Chem. Rev. 2006, 250, 2952; T. Gunnlaugsson, M. Glynn, G. M.
Tocci,P. E. Kruger, F. M. Pfeffer Coord. Chem. Rev. 2006, 250,
1
.2. Synthesis of H2:
Diacetylmonoxime (200 mg, 2 mmol) was dissolved in 30 mL of
ethanol in a 100 mL round bottom flask. To the solution, 2ꢀ
hydroxybenzohydrazide (300 mg, 2 mmol) was added and the
solution was refluxed overnight with continuous stirring. The
resultant solution was evaporated in vacuum which yield 367 mg
H2 as white solid.
3
094; D. S. Kim and J. L. Sessler Chem. Soc. Rev. 2015, 44, 532; S.
K. Kim and J. L. Sessler Acc. Chem. Res. 2014, 47, 2525.
3
P. Connet Fluoride 2007, 40, 155; R. G. Foulkes Fluoride 2007, 40,
229; R. J. Carton Fluoride 2006, 39, 163; S. Matsuo; K. Kiyomiya
andM.Kurebe, Arch. Toxicol. 1998, 72, 798; D. Briancon Rev.
Rheum. 1997, 64, 78; K. L. Kirk In Biochemistry of the Halogens and
Inorganic Halides, Plenum: New York, 1991; E. B.Bassin, D. Wypij
andR. B. Davis Cancer Causes Control 2006, 17, 421; Y.Yu,
W.Yang, Z. Dong, C.Wan,J. Zhang, J. Liu, K. Xiao, Y. Huang and B.
Lu Fluoride 2008, 41, 134. (i) B. L. Riggs Bone and Mineral
Research, Annual 2, Elsevier, Amsterdam, 1984. (j) M. Kleerekoper,
Endocrinol. Metab. Clin. North Am., 1998, 27, 441.
M. A. G. T. Van Den Hoop, R. F. M. J. Cleven, J. J. Van Staden and
J. Neele, J. Chromatogr., A. 1996, 739, 241; M. C. Breadmore; A. S.
Palmer; M. Curran, M. Macka, N. Advalovic and P. R. Haddad Anal.
Chem. 2002, 74, 2112; J. P. Hutchinson, C. J. Evenhuis; C. Johns, A.
A. Kazarian, M. C. Breadmore, M. Macka, E.F. Hilder, R. M.Guijt,
G. W. Dicinoski and P. R. Haddad, Anal. Chem. 2007, 79, 7005.
C. B. Black, B. Andrioletti, A. C. Try, C. Ruiperez and J. L. Sessler
J. Am. chem. Soc. 1999, 121, 10438; M. Takeuchi,T. Shioya and T.
M. Swager Angew. Chem. Int. Ed. 2001, 40, 3372; T. Mizuno, W. –
H. Wei, L. R. Eller and J. L. Sessler J. Am. Chem. Soc. 2002, 124,
1134; D. A.Jose, D. K. Kumar, B. Ganguly and A. Das Org. Lett.
1
1
2
2
0
5
0
5
ꢀ
1
Yield: 78 %; m.p.: 276ꢀ279 ºC; FTꢀIR (νmax/cm ,KBr): 3283 (w),
3104 (br), 2717(m), 2575(m), 1927(w), 1811(w), 1651(s),
1
1
5
547(s), 1495(w), 1452(s), 1373(s), 1299(s), 1227(s), 1150(s),
101(w), 1023(m), 985(w), 944(s), 828(w), 745(s), 619(s),
65(m), 503(m), 456(m), 414(w); H NMR (DMSOꢀd , 400
1
70
75
4
5
6
MHz, δ in ppm): 11.69(s, 1H) , 11.59(s, 1H), 11.28(s, 1H), 7.94ꢀ
7.92 (d, J = 7.96 Hz, 1H), 7.73(s, 1H), 7.38ꢀ7.36 (d, J = 7.16 Hz,
1
H), 6.98ꢀ6.92 (m, 1H), 2.22ꢀ2.12(d, J =39.68, 3H), 2.09ꢀ1.99 (d,
1
3
J = 36.52, 3H);
C NMR (DMSOꢀd , 100 MHz, δ in ppm) :
6
1
1
62.16, 156.78, 155.15, 131.33, 120.33, 40.22, 40.02, 39.81,
1.70, 9.85; Elemental analysis:Found: C, 56.28; H, 5.22; N,
17.77% Calc. for C H N O : C, 59.15; H, 5.87; N, 18.83%;
UVꢀVis: λmax(DMSO)/ nm280, 375.
1
1
13
3
3
8
8
9
9
0
5
0
5
2
004, 6, 3445; D. E. Gomez, L. Fabbrizzi and M. J. Licchelli J. Org.
Chem. 2005, 70, 5717; M. Cametti and K. Rissanen Chem. Commun.
009, 2809; T. W. Hundall, C. –W. Chiu and F. P. Gabbai Acc.
1
.3. Anion binding study:
2
Chem. Res. 2009, 42, 388; S. –D. Jeong, A. NowakꢀKrol, Y. Kim, S.
–J. Kim, D. T. Gryko and C. –H. Lee Chem. Commun. 2010, 46,
The quantitative anion binding study was performed with the help
of UVꢀVis spectroscopy as DMSO solution. The receptor H
solutions were titrated by adding known quantities of
concentrated solution of the anions in question. The anion
solutions used to effect the titrations contained the receptor at the
same concentration as the receptor solutions into which they were
being titrated so as to nullify the dilution effect. After getting the
absorption data, the binding constant is evaluated by using
Connor equation:
3
0
8
737; C. R. Wade, A. E. J. Broomsgrove, S. Aldridge and F. P.
Gabbai Chem. Rev. 2010, 110, 3958; P. Sokkolingam and C. –H. Lee
J. Org. Chem. 2011, 76, 3820; S. P. Mahanta, B. S. Kumar, S.
Baskaran, C. Sivasankar and P. K. Panda Org. Lett. 2012, 14, 548; P.
Das, M. K. Kesharwani, A. M. Mandal, E. Suresh, B. Ganguly and A.
Das Org. Biomol. Chem. 2012, 10, 2263; A. Ayodogan, A. Koca, M.
K. ꢂener and J. L. Sessler Org. Lett. 2014, 16, 3764; I. Saha, J. H.
Lee, H. Hwang, T. S. Kim and C. ꢀ H. Lee Chem. Commun. 2015,
3
5
5
1, 5679; F. Keymeulen, P. D. Bernardin, I. Giannicchi, L.
Galantini, K. Bartik and A. Dalla Cort Org. Biomol. Chem. 2015,
3, 2047.
1
[
ꢀ − ꢀꢁ] ꢃ ꢅ ∆ɛ[ꢇ]
6
M. Cametti, A. D. Cort and K. Bartik ChemPhysChem 2008, 9, 2168;
M. Goursaud, Paolo De Bernardin,A. D. Cort, K. Bartik and G.
Bruylants. Eur. J. Org. Chem. 2012, 3570; L. Trembleau, T. A. D.
Smith and M. H. Abdelrahman Chem. Commun. 2013,49, 5850.
F. P. Schmidtchen and M. Berger Chem. rev. 1997, 97, 1609; . P.
Schmidtchen Coord. Chem. Rev. 2006, 250, 2918.
ꢄ
ꢆ
=
ꢂ
1 + ꢅ [ꢇ]
ꢆ
where ꢀ , ꢀ: Measured absorbance of the substrate in absence 100
°
4
0
and in presence of guest; ꢃ : Total host concentration (M);ꢈ[ꢇ]:
Guest concentration (M);ꢈꢅ : Binding constant (M );ꢈ∆Ɛ: Molar
absorptivity of the hostꢀguest solution,ꢈꢂ: Path length.
The corresponding BenesiꢀHildebrand plot is
7
8
ꢄ
ꢀ
1
ꢆ
M. Kigga and D. R. Trivedi Journal of Fluorine Chemistry 2014,
1
60, 1; Y. Zhou, J. F. Zhang and J. Yoon Chem. Rev. 2014, 114,
5511; M. A. MartínezꢀAguirre and A. K. Yatsimirsky J. Org. Chem.
015, 80, 4985.
C. B. Rosen, D. J. Hansen and K. V. Gothelf Org. Biomol. Chem.
013, 11, 7916; D. A. Jose, P. Kar , D. Koley, B. Ganguly , W.
1
05
1
1
1
2
=
+
[
ꢀ − ꢀꢁ] ꢃ ꢅ ꢂ∆Ɛ[ꢇ] ꢃꢄꢂ∆Ɛ
9
ꢄ
ꢆ
2
From the ratio of the slope and intercept of the BenesiꢀHildebrand
plot the binding constant K can be evaluated.
Thiel, H. N. Ghosh and A. Das Inorg. Chem. 2007, 46, 5576; H.
Tong, G. Zhou, L. Wang, X. Jing, F. Wang and J.
Zhang Tetrahedron Lett. 2003, 44, 131; B. Taner, O. Alici and P.
Deveci Supramolecular Chemistry 2014, 26, 119; C. B. Rosen, D. J.
Hansen and K. V. Gothelf Org. Biomol. Chem. 2013, 11, 7916.
0 F. G. Bordwell and G. Z, Ji J. Org. Chem. 1992, 57, 3019; F. G.
Bordwell Acc. Chem. Res. 1988, 21, 456.
1
5
4
5
110
a
Acknowledgements
1
1
This work was financially supported by SERB, Department of
Science and Technology, New Delhi. SPM thanks Tezpur
University for financial support in the form of a seed grant.
1
15
1
J. P. Naskar, C. Biswas, L. Lu and M. Zhu J. Chem. Crystallogr.
2011, 41, 502; F. Vláčil Collect. Czech. Chem. Commun. 1961, 26,
6
50.
1
2
J.ꢀP. Costes, C. Duhayon Eur. J. Inorg. Chem. 2014, 4745.
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 |
7

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M. A. Spackman and D. Jayatilaka CrystEngComm 2009, 11, 19; J. J.
McKinnon, M. A. Spackman and A. S. Mitchell Acta Cryst. 2004.
B60, 627.
T.
A. Enache and
A.
M. OliveiraꢀBrett
Journal of
5
0
5
0
Electroanalytical Chemistry 2011, 655 , 9; I. Novak1, Š. Komorskyꢀ
Lovrić2, S. Žunec and A. Vrdoljak Int. J. Electrochem. Sci. 2013, 8,
9
818; Keith J. Winstanley, A. M. Sayer and D. K. Smith Org.
Biomol. Chem. 2006, 4, 1760.
1
1
5 K. A. Connors, In Binding Constant Determination; Wiley, New York,
1987. (b) C.Schalley and K.Hirose, In Analytical Methods in
Supramolecular Chemistry; WileyꢀVCH, 2007. (c) H. A. Benesi and
J. H. Hildebrand J. Am. Chem. Soc. 1949, 71, 2703.
1
1
2
6 B. S. Berlett, R. L. Levine, and E. R. Stadtman Anal. Biochem. 2000,
2
87, 329.
8
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194x865mm (96 x 96 DPI)