A halogen-bonding foldamer molecular film for selective reagentless anion sensing in water

Article abstract of DOI:10.1039/C9CC00335E

We describe self-assembled monolayers of novel halogen-bonding and hydrogen-bonding foldamer receptors capable of selectively recruiting perrhenate, iodide and thiocyanate in water. Unprecedented anion sensing via impedance-derived capacitance spectroscopy enables subsequent sensitive and selective anion detection without the need for a redox probe. Importantly, the sensing of any anion should be possible using this novel electrochemical approach.

Full text of DOI:10.1039/C9CC00335E

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DOI: 10.1039/C9CC00335E
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A halogen-bonding foldamer molecular film for selective
reagentless anion sensing in water
Robert Hein, Arseni Borissov, Martin D. Smith, Paul D. Beer* and Jason J. Davis*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
We describe self-assembled monolayers of novel halogen-bonding sensing15-22, particularly sensing of anions, remains largely
1
9-22
and hydrogen-bonding foldamer receptors capable of selectively unexplored.
In its standard form EIS assays require the pre-
recruiting perrhenate, iodide and thiocyanate in water. doping of the solution with an excess of signal amplifying redox
3
-/4-
2+/3+
Unprecedented anion sensing via impedance-derived capacitance probe, usually Fe(CN)
6
or Ru(NH
)
3 6
. The use of high
spectroscopy enables sensitive and selective anion detection background concentrations of such multiply charged
without the need for a redox probe. Importantly, the sensing of any complexes, some of which may adsorb, is a major drawback
anion should be possible using this novel electrochemical when seeking to sensitively monitor low levels of specific ion
approach.
binding. The omission of such transducers enables a more facile
analysis of real-world samples and additionally allows for
electrode potentials to be chosen with more flexibility.
Although enormously important, anion recognition and, in
particular, sensing in pure water remains both challenging and
underdeveloped.1 Recently we demonstrated that halogen
bonding (XB) water-soluble anion receptors can complement or
outperform more traditional receptors based on hydrogen
In the absence of a redox transducer the change in interfacial
capacitance can be used as a transducer of ion binding as
,2
16,17
preliminarily demonstrated for cation sensing.
Selective
anion sensing, via this strategy is, to the best of our knowledge,
unprecedented.
3
-6
bonding (HB) or simple electrostatic interactions. However,
XB-mediated anion sensing in water remains rare. The
4
detection of large, charge-diffuse anions such as perrhenate
Based on our previously reported tetratriazole-foldamer23 we
synthesised novel preorganised, water-soluble foldamers
-
(
ReO
4
), is particularly challenging, yet of major interest, since
-
-
7
both ReO
TcO
4
and TcO
4
are used as radiopharmaceuticals and
1
.XB/HB and 2.XB/HB (Fig. 1, ‡) capable of anion recognition in
-
4
is a major hazardous pollutant originating from nuclear
water. It should be noted that anion binding in pure water
power generation.8
2
utilising such neutral, acyclic receptors is extremely rare. The
Sensing via electrochemical techniques is typically rapid,
sensitive, environmentally flexible and scalable. Of these,
electrochemical impedance spectroscopy (EIS), in which a small
amplitude alternating current with varying frequencies is
applied to the electrode at a constant potential, is a particularly
sensitive means of reporting on steric, electrostatic or dielectric
changes associated with an electrode-confined target capture
event. It requires no synthetic integration of a reporting group
synthesis via multiple click reactions is described in the
Supporting Information S2. Incorporation of a disulfide anchor
group into 1.XB/HB facilitates SAM formation via exposure of
clean gold disk electrodes to solutions of 1.XB/HB (in ACN/H
2
O
1
:1) overnight to produce 1.XB/HBSAM (Fig. 2).
X-ray photoelectron spectroscopy (XPS) of 1.XB/HBSAM revealed
the presence of iodine in the film only for 1.XBSAM with
otherwise identical elemental composition for both SAMs
(e.g. ferrocene) and leads to minimal perturbations of the
1
.XB/HBSAM and excellent agreement with theoretical
electrode interface. Although EIS based sensing of large
predictions (Fig. S5-10 and Tables S1-3).
9
-14
biomolecules has gained much attention , impedimetric ion
Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ,
U. K. E-mail: paul.beer@chem.ox.ac.uk, jason.davis@chem.ox.ac.uk
†
Electronic Supplementary Information (ESI) available: Details on methods and
synthetic procedures as well as further characterization of the interface and sensor
performance. See DOI: 10.1039/x0xx00000x
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O
O
N
O
O
O
N
O
11
mol/cm2 for 1.XBSAM and 1.HBSAM, respectively (as
O
O
O
O
View Article Online
DOI: 10.1039/C9CC00335E
determined by reductive stripping voltammetry, Fig. S13). This
corresponds to a molecular footprint of approx. 2 nm , which is
in good agreement with the size of 1.XB/HB and is indicative of
well-packed, ordered SAMs. This was further confirmed by a
lack of Faradaic activity in the presence of 10 mM Fe(CN)
6
(Fig. S14) where the films block access of the redox probe to the
electrode.
2
N
N
N
N
N HN
O
O
NH N
O
O
O
O
O
O
O
O
O
O
3
-/4-
X
X
X
X
O
O
O
O
NH N
N HN
N
N
160
140
120
100
1
.XBSAM
1
.XBSAM + 50 mM ReO4-
O
R
O
1
.XB (R = R1, X = I)
.HB (R = R1, X = H)
8
0
R1 =
R2 =
N
O
H
1
S
S
60
2
.XB (R = R2, X = I)
.HB (R = R2, X = H)
4
0
0
0
O
O
2
O
O
2
Fig. 1 Chemical structures of halogen and hydrogen bonding anion receptors 1.XB/HB
and 2.XB/HB.
+
ReO4-
-50
0
50
100
150
200
250
300
350
The thickness of the SAMs was determined by ellipsometry as
-
C' (nF)
3
.22 ± 0.21 nm and 3.51 ± 0.40 nm, respectively, consistent with
the formation of a monolayer. The presence of the PEG-groups Fig. 3 Capacitive Nyquist plots of 1.XBSAM in the absence and presence of 50 mM ReO
in 1.XB/HBSAM induces formation of hydrophilic, hydrated
SAMs, as supported by water contact angles of 60° and 55° (Fig.
S11), in good agreement with prior observations at PEG-SAMs.
4
-.
Measurements were performed at OCP (≈ 0 V) in the presence of 100 mM electrolyte (x
NaCl + y NaReO , x + y = 100 mM).
4
2
4
EIS at open-circuit potential (OCP, ≈ 0 V) in the absence of any
redox probe leads to the expected impedimetric signatures
devoid of any characteristic charge-transfer features (Fig. S15A)
and the impedance is largely unresponsive to all analytes
(anions) used herein (Fig. S15A and Fig. S16). However, if
capacitive analysis is carried out the resulting capacitive Nyquist
and Bode plots (Fig. 3 and Fig. S17) are clearly responsive to the
presence of analyte. The film capacitance C, which is a sensitive
function of anion concentration, can be obtained as the x-
intercept of the hemispherical region in the capacitive Nyquist
S T
plots or from data fitting to a R (C[R Q]) equivalent circuit
where R is the solution resistance, C the film capacitance, R a
S
T
2
5
translational resistive term arising from ionic ingress and Q a
constant phase element (Fig. S15). The film capacitance of
1
.XB/HBSAM in the absence of any target anion was determined
2
2
as 4.85 ± 0.36 µF/cm and 4.83 ± 0.72 µF/cm , respectively. As
can be seen in Fig. S18, there is only a small effect of the
electrolyte concentration on C, indicating that, as expected, the
Fig. 2 Schematic representation of 1.XBSAM on a gold electrode. Surface immobilization
is achieved via a multivalent disulfide anchor (black) to immobilize the foldamer anion measured capacitance is dominated by the SAM and not the
binding motif (red/purple) onto the electrode. Hydration of the film as well as electrolyte/solution. Utilising a simple Helmholtz model (plate
preorganisation of the triazole binding motifs is induced by PEG groups (blue).
capacitor, eq. 1) and the ellipsometrically determined film
r
thickness, d, the dielectric constant ε of 1.XB/HBSAM in the
absence of target analyte can be calculated as 17.6 and 19.2,
respectively.§
All electrochemical experiments were carried out in pure
aqueous solution containing 100 mM NaCl as supporting
electrolyte. Sodium chloride was chosen as electrolyte because
it does not interact with the foldamer and is present in similar
concentrations in biologically and environmentally relevant
samples. As expected, the foldamer SAMs are not electroactive
휀0 ∗ 휀푟 ∗ 퐴
퐶 =
(1)
푑
Although the detailed physicochemical origins of the
capacitance change in the presence of a target anion are
currently under investigation, we directly attribute the increase
(
Fig. S12) and are densely packed with a molecular surface
-11
2
-
coverage of (8.85 ± 1.70) × 10 mol/cm and (6.40 ± 1.60) × 10
2
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r
in capacitance of XB and HB foldamer SAM upon anion binding indicating that the change in capacitance (due to change in ε )
to an increased film dielectric constant (eq. 1). This change is has a significant non-electrostatic compDoOneI:n10t..1F0o39r/Ce9xCaCm0p0l3e3,5aE
fully consistent with the introduction of a charged guest species large increase in capacitance of up to 35% (change of ε from
r
and a concomitant hydration of the hydrophobic core (i.e. 17.6 to 23.8) is observed for perrhenate at 1.XBSAM whereby
binding site) of the SAM. It is important to note that this change iodide and thiocyanate induce a much smaller change (≈ 15%).
arises from a specific binding event; exposure of non-receptive
interfaces (e.g. alkanethiol SAMs) to target anions under the
same conditions induces negligible change in the capacitance
퐾 ∗ [퐴푛푖표푛]
휃 = 1
+ 퐾 ∗ [퐴푛푖표푛]
(2)
The limit of detection (LOD) of the 1.XBSAM sensor was
determined to be 28, 14, and 42 µM for perrhenate, iodide and
thiocyanate, respectively, indicating highest sensitivity for
iodide. The 1.HBSAM sensor was predictably and significantly less
sensitive with respective LOD values of 80, 47 and 113 µM for
perrhenate, iodide and thiocyanate (Table 1 and Supporting
Information S4), highlighting the superiority of the halogen-
bonding interface.
(
<2%). This is further corroborated by the fact that the two
structurally identical films 1.XB/HBSAM display a significantly
different response to target anions which can only arise from
the change in the specific binding site, proving that the anion
indeed binds to the specifically engineered receptors rather
than otherwise associating/interacting with the interface.
1
.XBSAM
.HBSAM
40
30
20
10
0
1
Table 1 Limits of detection and binding constants of various anions to 1.XB/HBSAM
.
1
.XBSAM 1.HBSAM
a
-1
b
a
-1
b
Anion
K (M )
LOD (µM)
K (M )
LOD (µM)
-
ReO
I-
4
231
362
170
/
/
/
28
14
42
/
/
/
11
66
61
/
/
/
80
47
113
/
/
/
SCN-
-
ClO
Br-
4
-
NO
3
a
Determined from fitting to Langmuir model (eq. 2, Fig. 5). b For further details see
0
10
20
30
40
50
-
Supporting Information S4. / – no binding (negligible increase in C). Estimated
errors for K and LOD: <20%.
[
ReO ] (mM)
4
Fig. 4 Normalized capacitance increase of 1.XB/HBSAM at OCP (≈ 0 V) in the presence of
-. Fits were obtained according to a Langmuir adsorption
Importantly, exposure of 1.XB/HBSAM to other anions such as
increasing amounts of ReO
4
model (eq. 2). Error bars represent one standard deviation across three independent bromide, perchlorate or nitrate at concentrations > 10 mM did
electrodes.
not result in any significant change in the capacitance indicating
that both XB and HB foldamer SAMs only selectively bind the
A more detailed analysis of 1.XBSAM film capacitance confirms a
charge-diffuse anions iodide, perrhenate and thiocyanate over
response which is greatest for perrhenate (Fig. 4) but also
other similar anions such as bromide or perchlorate. A
significant for iodide or thiocyanate (Fig. S19A). The respective
comparative solution phase binding analysis of the water
isotherms were fitted to a simple Langmuir adsorption model
soluble 2.XB/HB receptors was carried out in water by
(
eq. 2, Table 1 and S4) where 휃 is the fractional occupancy of
isothermal titration calorimetry (ITC, Tables S5-6)‡, where a
higher binding affinity for all tested anions, but lower guest
selectivity, was observed. Furthermore, 2.XB forms 2:1 host-
guest complexes in solution. Altered enthalpic and entropic
contributions, together with steric constraints on 2:1 binding,
reduce anion affinity to the foldamer SAMs but enable better
discrimination between guests than is possible in solution. For
example, while both bromide and iodide strongly bind to
the receptive sites and K the binding constant between the
2
receptor and the anion. In all cases a good fit (R > 0.974) was
obtained and the binding constants determined to be 231, 362
and 170 M-1 for perrhenate, iodide and thiocyanate,
respectively (Table 1). Addition of these anions to 1.HBSAM also
induces an increase in capacitance (Fig. 4 and S19B), albeit with
a significantly smaller response for all anions, in particular at
low concentrations. This is a reflection of the lower affinity of
2
.XB/HB in solution (Table S5-6), films of 1.XB/HBSAM are able
-1
all anions to 1.HBSAM, with K = 11, 66 and 61 M for perrhenate,
to discriminate between these and also between perchlorate
and perrhenate (see Table 1 and Supporting Information S4). It
should also be noted that solution-phase studies reveal no
influence of the counterion on anion binding.‡
Significantly, due to reversibility of the non-covalent host-guest
interaction, the capacitive response of these films is not only
selective but also reversible, enabling sensor re-use (Fig. S20)
and potentially continuous, real-time monitoring of anions
under flow conditions.
2
iodide and thiocyanate, respectively (R > 0.991, Table 1 and
S4). This decreased affinity is in agreement with anion binding
constants of 2.XB/HB in solution (vide infra). At high anion
concentrations the responses of 1.XB/HBSAM converge, in good
agreement with the Langmuir adsorption model (binding site
saturation). Slight deviations from an ideal Langmuir isotherm
for iodide might be attributed to its electroactivity at moderate
potentials.§§ Interestingly, the maximum increase in
capacitance (at saturation) differs for these monovalent anions
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§
§ While all measurements were performed at VOieCwPArti(culesOunalilnlye
In contrast to standard Faradaic EIS where the electrode
potential is restricted to the formal potential and solution phase
conditions (solubility) suitable for the redox probe (e.g.
between -50 to +50 mV) and iodide oxidation only occurs at 0.5 V
DOI: 10.1039/C9CC00335E
the onset of faradaic activity at lower potentials might be
observed at high iodide concentrations. It should be noted that
the OCP of the system might change upon addition of target
3
-/4-
Fe(CN)
6
) the herein presented non-Faradaic capacitive
method can be performed at a freely chosen electrode potential anion, however this change is not always monotonic nor
analytically useful.
and in principle in any solvent. The former is relevant for sensing
of analytes such as iodide (achieved herein) whose moderate
oxidation potential would overlap with the most commonly
1
2
S. Kubik, Chem. Soc. Rev., 2010, 39, 3648-3663.
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Ed., 2016, 55, 1974-1987.
3
-/4-
used Fe(CN)
6
in Faradaic EIS. Not only does the free choice
of electrode potential allow measurement conditions that are
more compatible with the analyte or interface of choice but
could potentially enable modulation of (an)ion binding strength
and selectivity through specific surface polarisation. In cases
where receptor surface density is high (as it is here, see Fig. S21)
initial levels of impedance can also be high and thereafter
unresponsive to target.
3
4
5
6
7
8
9
M. J. Langton, S. W. Robinson, I. Marques, V. Félix and P. D.
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In summary, we have prepared and characterized a well-
defined self-assembled receptive interface capable of selective
and sensitive sensing of the environmentally and biologically
2
292.
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relevant anions ReO
4
, I and SCN .
To the best of our
knowledge, this work is the first example of 1)
1
1
0 Q. Xu and J. J. Davis, Electroanalysis, 2014, 26, 1249-1258.
1 J. S. Daniels and N. Pourmand, Electroanalysis, 2007, 19,
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1
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applicable to the analysis of host-guest recognition within
molecular films without the synthetic need to integrate a redox
or optical transducer or to pre-dope the analyte solution with
an excess of redox probe. Importantly, the sensing of any anion
should be possible with this novel approach, if the appropriate
anion receptor is employed. Furthermore, we believe that this
methodology is not only highly relevant for anion sensing
applications in real-life samples, but can also serve as a
powerful tool to investigate host-guest interactions at
interfaces by avoiding drawbacks commonly associated with
Faradaic techniques. We are currently seeking to apply this
strategy for a variety of ion sensing applications, in particular
the sensing of ion-pairs or zwitterionic species (challenging
using Faradaic methods).
1
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AB is grateful to the EPSRC Centre for Doctoral Training in
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Conflicts of interest
There are no conflicts to declare
2
2
Notes and references
‡
2
§
Synthesis and detailed solution-phase anion binding studies of
.XB/HB and similar receptors have been reported separately.27
As expected for such a polar, hydrophilic film, these dielectric
constants are much larger than for a simple alkylated film.
4
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