Tracking a photo-switchable surface-localised supramolecular interaction via refractive index

Article abstract of DOI:10.1039/c5tc03774c

As supramolecular chemistry evolves, from the design of interactions in the solution and the solid state to applications at surfaces, there is a need for the development of analytical techniques capable of directly interrogating surface-localised supramolecular interactions. We present a proof-of-concept integrated optical Bragg grating sensor, capable of evanescently detecting small changes in refractive index at infrared wavelengths within a microfluidic system. The high spectral fidelity of the Bragg gratings combined with precise thermal compensation enables direct monitoring of the surface throughout the experiment, enabling the sensor to probe changes in situ and in real-time during surface preparation and chemical modification, and then to follow the progress of a dynamic surface-localised supramolecular interaction. In this study the sensor is assessed through the investigation of a photo-switchable inclusion complex between an azobenzene-functionalised surface and cyclodextrin in aqueous solution. The ability to investigate supramolecular interactions directly in real-time upon a planar surface via refractive index offers a valuable new tool in the understanding of complex dynamic supramolecular systems.

Full text of DOI:10.1039/c5tc03774c

View Article Online
View Journal
Journal of
Materials Chemistry C
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: R. M. Parker, D. J.
Wales, J. C. Gates, P. G. R. Smith and M. C. Grossel, J. Mater. Chem. C, 2016, DOI: 10.1039/C5TC03774C.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/materialsC

Please do not adjust margins
Journal of Materials Chemistry C
Page 1 of 9
View Article Online
DOI: 10.1039/C5TC03774C
Journal Name
ARTICLE
Tracking a photo-switchable surface-localised supramolecular
interaction via refractive index
Received 00th January
20xx,
Richard M. Parker,a,b* Dominic J. Wales,a,b James C. Gates,b Peter G. R. Smithb and Martin C.
Grossela
As supramolecular chemistry evolves, from the design of interactions in the solution and the solid state to applications at
surfaces, there is a need for the development of analytical techniques capable of directly interrogating surface-localised
supramolecular interactions. We present a proof-of-concept integrated optical Bragg grating sensor, capable of evanescently
detecting small changes in refractive index at infrared wavelengths within a microfluidic system. The high spectral fidelity of
the Bragg gratings combined with precise thermal compensation enables direct monitoring of the surface throughout the
experiment, enabling the sensor to probe changes in situ and in real-time during surface preparation and chemical
modification, and then to follow the progress of a dynamic surface-localised supramolecular interaction. In this study the
sensor is assessed through the investigation of a photo-switchable inclusion complex between an azobenzene-functionalised
surface and cyclodextrin in aqueous solution. The ability to investigate supramolecular interactions directly in real-time upon
a planar surface via refractive index offers a valuable new tool in the understanding of complex dynamic supramolecular
systems.
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
been compatibly combined, however the challenge lies in
developing robust methods for real-time interrogation of
dynamic self-assembly at the surface, both non-destructively
1. Introduction
Through the investigation of non-covalent intermolecular
interactions between molecules, supramolecular chemistry has
applied the principles of dynamic self-assembly to create
complex nano-scale architectures,1 including molecular
switches2 and machines.3–5 While supramolecular chemistry has
traditionally focused upon the manipulation of molecules in the
solution phase, leading to a diverse library of intricate
structures evolving towards numerous potential applications,6
there is an increasing drive to link developments in the solution
phase with solid-state crystal engineering7 through surface-
based supramolecular chemistry.8–10
and in situ.
A wide body of analytical techniques has been developed to
probe the liquid/solid interface at surfaces,13 a subset of which
have been applied to the study of supramolecular interactions
at a surface. Indirect measurements, such as monitoring
changes in the concentration of a component in solution14 or
macroscopic changes in hydrophobicity of a surface2 can reveal
much about the underlying supramolecular chemistry;
nevertheless there remains a need for direct, real-time
measurement. While one option is fluorescence,15 the
requirement for a fluorescent centre brings some limitations in
terms of the types of interactions that can be studied, in
addition to that of photobleaching and the difficulty in
distinguishing signals originating at the surface from the
Surface chemistry has been utilised throughout nanoscience
for assembling layers of molecules onto a substrate; often
through the use of a self-assembled monolayer (SAM).11 This
approach is compatible with supramolecular systems, with the
‘artificial molecular muscle’ reported by Liu et al representing a
notable example capable of performing mechanical work.12
Much of supramolecular and surface-based chemistry have
surrounding
media.
Surface-enhanced
Raman-based
techniques have also shown promise in the detection of
supramolecular interactions,16 however limitations in the use of
structured substrates and the difficulty in resolving individual
peaks within a complex host-guest system restricts their
application. Thin film techniques such as ellipsometry and the
quartz crystal microbalance (QCM), in addition to detecting the
deposition of covalent monolayers,17 have been applied to the
detection of the layer-by-layer deposition of supramolecular
polymer films18 and nanoparticle assemblies19 or for
supramolecular-based detection via a surface thin-film.20,21
However little has been reported using these techniques for the
a.Chemistry Department, University of Southampton, Highfield, Southampton, SO17
1BJ (United Kingdom)
b.Optoelectronics Research Centre, University of Southampton, Highfield,
Southampton, SO17 1BJ (United Kingdom)
* E-mail: rmp53@cam.ac.uk
Additional data related to this publication is available at the University of
Southampton data repository (http://dx.doi.org/10.5258/SOTON/385310).
Electronic Supplementary Information (ESI) available: solution-based NMR studies of
the photo-switchable azobenzene/α-CD complex, integrated optical Bragg grating
fabrication and interrogation methods, and additional surface-binding studies; with
supporting figures. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Journal of Materials Chemistry C
Page 2 of 9
ARTICLE
Journal Name
photo-switchable molecular storage within mesoporous silica
View Article Online
nanoparticles,14 monitoring was achievedDvOiaI: t1h0.e10b3u9l/kC5reTCle0a3s7e74oCf
fluorescently-tagged β-CD, rather than direct investigation of
this photo-controlled interaction. Furthermore, detection of
organic vapours has been reported using an optical Bragg
grating refractometer, dip-coated with an allylated cyclodextrin
thin-film.33
2. Experimental details
2.1 Optical sensor design and interrogation.
A Bragg grating is an optical component that acts as a
wavelength-selective reflector, with the characteristic Bragg
peak reflected at a wavelength dependent on both the effective
refractive index (neff) of the waveguiding media and the intrinsic
period of the grating (Equation S1, ESI). We have previously
reported the fabrication of an integrated-optical Bragg grating
device by direct UV-writing into the photosensitive glass core of
a planar silica-on-silicon substrate.34,35 The central Bragg
wavelength (λB) is determined by applying a Gaussian-fit to the
reflected spectrum of the grating and interrogated to sub-
picometre resolution via optical fibre, with low insertion loss.
This all-optical device is capable of precise refractive index
measurement at infrared wavelengths (1535 – 1575 nm, Figure
2). The combination of high spectral fidelity and precise
temperature compensation enabled changes in the refractive
index of the analyte (nanal) to be detected to 1 part in 10-6.36 We
have demonstrated that such an integrated optical
refractometer can be incorporated within a microfluidic device
compatible with a wide range of solvent systems, including
strong acids and bases,37 where it can monitor in real-time the
formation of a self-assembled monolayer at the sensor
surface.38
Fig. 1 A schematic of the azobenzene-modified self-assembled monolayer (top)
formed on the surface of the Bragg grating sensor (bottom). The formation of the
inclusion complex between the azobenzene-modified surface and an aqueous
solution of α-cyclodextrin can be dynamically triggered through
photoisomerisation of the azobenzene moiety.
study of molecular-scale, supramolecular monolayer surfaces.
An alternative parameter to interrogate is the refractive
index of an optical mode adjacent to the surface; surface-
localised refractive index measurement (typically via surface
plasmon resonance, but also interferometry, ring resonators or
gratings) has the benefit of being label-free and has been
successfully applied to biological and to a lesser extent,
chemical sensing.22–26 However, it remains highly challenging to
separate a subtle change in surface-localised refractive index
induced by a supramolecular interaction from fluctuations in
refractive index originating from environmental phenomena
(principally temperature or concentration).
For this work, an integrated optical waveguide circuit
containing a series of four Gaussian-apodised Bragg gratings
was fabricated. An 18 μm deep channel was etched into the
silica above three of the Bragg gratings, mechanically polished
and sputtered with a thin-film of tantalum pentoxide (80 (± 4)
nm) to increase sensitivity.36 The Bragg gratings within the
etched region were used for sensing, while the fourth unetched
grating acted as an independent reference for physical
parameters,36 principally temperature (Figure S4, ESI). By
exposing the evanescent field of the waveguided optical mode
in this way, changes in the refractive index of the surface-
localised environment could be detected by the corresponding
shift in the peak Bragg wavelength. Figure 2c demonstrates this
measured Bragg wavelength shift on addition of a series of bulk
analytes and also highlights the enhanced sensitivity arising
from the tantalum pentoxide over-layer. Temperature
referencing was achieved in situ through differential analysis of
the two orthogonal polarisations of the waveguide.39 This was
necessary to fully decouple minute changes in the surface-
localised refractive index from the thermo-optic properties
(dn/dT) of the solvent. A full description of the fabrication and
interrogation of the optical device can be found within the
Electronic Supporting Information.
Here we employ an integrated optical Bragg grating sensor,
capable of evanescently detecting small changes in refractive
index at infrared wavelengths, with precise localised thermal
compensation. In order to critically assess the efficacy of
refractive index measurement as a method to directly probe
surface-localised supramolecular interactions, we chose to
target the well-understood photo-switchable inclusion complex
between aqueous α-cyclodextrin (α-CD) and
a surface-
immobilised azobenzene (Figure 1). This photo-switchable host-
guest interaction has been used to form a switchable
rotaxane,27,28 to reversibly immobilise nanotubes,29 to fabricate
hydrogels that undergo reversible gelation in solution,30 and
even to induce macro-scale hydrogel assembly.31,32 While such
behaviour has previously been exploited in the development of
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Journal of Materials Chemistry C
Page 3 of 9
ARTICLE
Journal Name
View Article Online
DOI: 10.1039/C5TC03774C
Fig. 2 (a,b) The integrated optical device consisted of four spectrally distinct Bragg gratings; an un-etched physical reference (*, λB = 1538nm) and three ‘sensor’ gratings
(λB ≈ 1546, 1556, 1566 nm) distributed along a linear waveguide. The reflected spectrum of the integrated optical device is plotted in air (n = 1.00, solid line) and in
water (n = 1.33, dashed line) both (a) logarithmically and (b) as an extract of the data on a linear scale, showing the Gaussian profile of the Bragg peaks and low optical
noise. The red line in (a) represents the background reflection spectrum from the erbium emission of the broadband source alone and it is this profile combined with
reduced scattering loss that leads to the increase in the peak height in (b). (c) The sensitivity to bulk analyte refractive index (nanal) as measured by the average Bragg
wavelength shift of the ‘sensor’ gratings resulting from changes in the effective refractive index (∆neff) of the waveguide, for the transverse electric (
orthogonal, transverse magnetic ( ) optical modes. The dashed-lines correspond to the bare sensor, illustrating the enhancement from the deposition of an 80 nm thin
film of tantalum pentoxide (solid line); loss of guidance of the optical mode at a lower analyte refractive index is the cost of this increased sensitivity.
X, sensor) and the
O
the mixture under reflux for 3 hours. The reaction mixture was
acidified (conc. HCl) before it was extracted with diethyl ether
2.2 Synthetic methods.
Commercially available compounds and solvents were obtained (3 x 60 mL). The combined extracts were dried with magnesium
from Sigma-Aldrich, Fisher Scientific or Acros Organics and used sulfate, filtered and the solvent was removed in vacuo to yield
as supplied, without further purification. Ethanol was distilled a yellow solid (
over calcium sulfate and used immediately. Instrumentation is 1H NMR (MeOD) δ/ppm 4.72 (s, 2H, -OCH2C(O)), 7.04 (d, J=9.0
detailed in the Supplementary Information. Hz, 2H, Ar-H), 7.37 - 7.54 (m, 3H, Ar-H), 7.81 (dd, J=8.1, 1.37 Hz,
3
, 0.255 g, >99 % yield). MP: 180 °C (Lit:43 184 °C).
4-Phenylazophenol (1) was prepared in 71% yield by diazotising 2H, Ar-H), 7.87 (d, J=9.0 Hz, 2H, Ar-H). 13C NMR (MeOD) δ/ppm
aniline and coupling at the para- position of phenol, as 66.1 (CH2), 116.2 (Ar), 123.7 (Ar), 125.8 (Ar), 130.3 (Ar), 131.9
previously reported.40,41
(Ar), 148.8 (Ar), 154.2 (Ar), 162.1 (Ar) 172.3 (C(O)). IR: v/cm-1
Ethyl (4-phenylazophenoxyacetate) (2) 4-Phenylazophenol (
1
,
3068 (C-H aromatic), 2915 (C-H), 2700 broad (O-H), 1706 (C=O),
0.380 g, 1.90 mmol) was dissolved in acetone (silica dried, 60 1602, 1582 (C=C aromatic), 1501 (N=N), 1143 (C-N), 1085 (C-O).
mL), followed by potassium carbonate (1.658 g, 11.9 mmol) and MS (ES+, MeOH) m/z 257.1 (67.9% [M+H]+), 279.1 (95.2%,
the mixture was warmed until complete dissolution. To this [M+Na]+), 311.1 (100.0%, [M+Na+MeOH]+). UV-vis (MeOH):
stirred solution, ethyl bromoacetate (0.125 mL, 3.75 mmol) and λmax/nm 320.5, 450.5 (cis), 342.0 (trans). HRMS (ES+, MeOH)
sodium iodide (0.287 g, 1.9 mmol, in 4.0 mL acetone) were then calcd. for C14H13N2O3 [M+H]+ 257.0921, found 257.0918, calcd.
added. The reaction mixture was heated under reflux for 16 h. for C14H12N2O3Na [M+Na]+ 279.0740, found 279.0737.
The solvent was removed in vacuo to give an orange solid. This 4-Phenylazophenoxyacetyl
chloride
(4)
4-
was subsequently extracted into diethyl ether (3 x 40 mL) from Phenylazophenoxyacetic acid (3, 0.100 g, 0.39 mmol) was
water (40 mL), before drying with magnesium sulfate, filtering refluxed in thionyl chloride (5 mL, 68.5 mmol) overnight under
and removing the solvent in vacuo. The resultant solid was nitrogen. The remaining thionyl chloride was removed via
purified using column chromatography (50:50 diethyl distillation under vacuum (50 °C), to give a red solid. A
ether:light petroleum (40-60)) to give an orange solid (2, 0.307 quantitative yield was assumed and the product was used
g, 90% yield). MP: 66 °C (Lit:42 70 °C). 1H NMR (MeOD): δ/ppm immediately without further purification. MS (ES+, MeOH) m/z:
1.26 (t, J=7.1 Hz, 3H, -CH3), 4.23 (q, J=7.1 Hz, 2H, -OCH2), 4.77 (s, 271.2 (23.7 % [M+H]+), 293.2 (100.0 % [M+Na]+), 325.2 (53.2 %
2H, -OCH2C(O)), 7.05 (d, J=9.0 Hz, 2H, Ar-H), 7.39 - 7.53 (m, J=7.5 [M+Na+MeOH]+), 563.3 (13.7 % [2M+Na]+). MS (ES-, MeOH)
Hz, 3H, Ar-H), 7.83 (dd, J=8.2, 1.7 Hz, 2H, Ar-H), 7.87 (d, J=9.2Hz, m/z: 126.9 (100.0 %, [N-2H]-), 255.3 (92.9 %, [N-H]-), 256.5 (18.4
2H, Ar-H). 13C NMR (MeOD): δ/ppm 14.6 (CH3), 62.6 (CH2), 66.4 %, [N]•-), 269.2 (11.9 % [M-H]-), where ‘N’ represents the
(CH2), 116.2 (Ar), 123.7 (Ar), 125.8 (Ar), 130.3 (Ar), 131.9 (Ar), molecular ion
148.9 (Ar), 154.17 (Ar), 162.1 (Ar), 170.6 (C(O)). IR: v/cm-1 3068 carboxylic acid. ‘M’ represents the molecular ion of methyl (4-
(C-H aromatic), 2937 (C-H), 1726 (C=O), 1600 (C=C aromatic), phenylazophenoxyacetate), formed from the reaction of with
1495 (N=N), 1149 (C-N), 1077 (C-O). MS (ES+, MeOH) m/z 285.2 the methanol MS solvent. The formation of the methyl ester
(14.5%, [M+H]+), 307.1 (64.4%, [M+Na]+).
was not seen with and as such can be used as an indicator for
(4- the successful synthesis of
, 0.280 g, 0.971 mmol) was
3, formed from decomposition back to the
4
3
4-Phenylazophenoxyacetic
acid
(3)
Ethyl
4.
phenylazophenoxyacetate) (
2
dissolved in ethanol (40 mL). To this, an aqueous solution of
sodium hydroxide (56 mM, 40 mL) was added before heating
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Journal of Materials Chemistry C
Page 4 of 9
ARTICLE
Journal Name
View Article Online
DOI: 10.1039/C5TC03774C
Scheme 1 The synthetic pathway for 4-phenylazophenoxyacetyl chloride,
NaOH, ethanol, and (v) thionyl chloride. Inset: schematic and chemical structure of the macrocycle, α-cyclodextrin.
4
; (i) NaNO2, HCl, <5 °C, (ii) phenol, <5 °C, (iii) ethyl bromoacetate, K2CO3, NaI, acetone, (iv)
wavelength (λB) increased by 46 (± 4) pm during the attachment
of 3-APTES, with a further increase of 761 (± 5) pm upon
attachment of to the surface. This corresponds to an increase
3. Results and discussion
4
in analyte refractive index (∆nanal) of 5.1 (± 0.4) x 10-4 and 8.4 (±
0.1) x 10-3 respectively, giving a cumulative refractive index shift
of ~8.9 x 10-3 for the deposition of the azobenzene-terminated
SAM. This observed change in refractive index is attributed to
the displacement of ethanol at the surface with that of the
higher refractive index monolayer.38 The attachment process
was independently verified by the detection of an absorption at
348 nm wavelength from an analogously functionalised glass
slide, characteristic of the azobenzene moiety (Figures S1 and
S6, ESI).
Cyclodextrins are a family of macrocycles composed of glucose
oligosaccharides, forming a truncated cone-like structure with
hydrogen-bonding hydroxyl groups around the outer rim. They
have been demonstrated to form host-guest complexes with a
wide range of compounds, stabilising aromatic groups within
their hydrophobic interior cavity.44 It has been reported that
both the glucose-hexamer α-cyclodextrin (α-CD) and glucose-
heptamer β-cyclodextrin (β-CD) will readily accommodate an
azobenzene unit within this cavity.45 However, upon
photoisomerisation of the more stable and rod-like trans-
azobenzene to its bent cis-isomer the complex will dissociate.
This process is reversible and upon reverting to the trans-isomer
the complex can reform.45
The azobenzene-functionalised device was installed within
a casing mounted with both ultraviolet (λmax = 370 nm, ∆λ1/2
=
12 nm) and blue (λmax = 464 nm, ∆λ1/2 = 22 nm) LED light sources
(Pd = 40 mW); whereby switching between these two
wavelengths would trigger photoisomerisation of the
azobenzene surface without interference from ambient light or
heating, avoiding thermal relaxation of the azobenzene moiety.
A 10 mM aqueous solution of α-CD was added to the etched
well and the device was allowed to equilibrate for several
minutes under blue illumination. Then, upon switching to UV
exposure, an immediate decrease in refractive index was
observed that slowed over three minutes to give a well resolved
Bragg wavelength decrease of 14.2 (± 0.5) pm in water, equating
to a decrease in total analyte refractive index (∆nanal) of 2.8 (±
0.1) x 10-4. This decrease in refractive index corresponds to the
azobenzene switching to the cis-isomer, perturbing the dynamic
equilibrium at the surface towards free α-CD (note that
photoisomerisation within the complex itself is sterically
inhibited46). By reverting to blue illumination the refractive
index shift was reversed, restoring the Bragg wavelength to its
original value, but over a longer timescale (~6 minutes). The
longer timescale on return to the initial trans-isomer is both
consistent with that seen in the previously reported polymer
system and in solution,47 indicating that photoisomerisation of
the azobenzene is rate limiting. This cycle of assembly and
disassembly was repeatable, as illustrated in Figure 3.
The azobenzene motif was immobilised at the sensor
surface via covalent linkage to a self-assembled monolayer of
(3-aminopropyl)triethoxysilane (3-APTES). This process was
realised within a microfluidic flow cell, where reagents were
flowed through the micro-channel in series for both cleaning
and preparative steps, functionalising the surface in situ before
recontamination could occur. Following our reported
protocol,38 the etched micro-channel was enclosed within a
stainless steel mount, sealed with a Kalrez™ O-ring. This
microfluidic flow cell was networked in series via 400 µm bore
ethylene tetrafluoroethylene tubing with a manifold solenoid
valve that allowed for the controlled flow from up to six
reservoirs, pushed through the system by a solenoid diaphragm
pump (Figure S5, ESI). The pump rate and choice of reservoir
was automated with LabVIEW via a USB DAQ controller. The
sensor surface was cleaned by an automated series of washes
with water and acetone, followed by 5.0 M potassium
hydroxide to restore the hydroxyl surface (80 min). 3-APTES
(10% v/v in distilled ethanol, 12 h) was flowed over this freshly
prepared surface to deposit a self-assembled monolayer,
affording an amine-terminated surface which was subsequently
reacted with a flow of 4-phenylazophenoxyacetyl chloride, (4,
50 mg in 70 mL dimethylsulfoxide in the presence of <0.1 mL
triethylamine, 12 h). After each subsequent functionalisation of
the surface, the shift in Bragg wavelength was recorded in an
ethanol reference solution. It was found that the Bragg
While the magnitude of this refractive index change is
smaller than that observed for the formation of the dense
azobenzene monolayer, it is important to note that in the latter
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 4
Please do not adjust margins

Please do not adjust margins
Journal of Materials Chemistry C
Page 5 of 9
ARTICLE
Journal Name
View Article Online
DOI: 10.1039/C5TC03774C
Fig. 3 The Bragg wavelength shift for the azobenzene-APTES modified sensor surface in the presence of a 10 mM α-cyclodextrin solution (black circles, guideline traces
the five-point moving average). Reversible photo-switching was observed upon alternating exposure to light at 360-380 nm (‘UV’) and 440-480 nm wavelength (‘blue’).
Thermal compensation was achieved through a first order approximation, derived from differential analysis of the two orthogonal polarizations of the waveguide. For
comparison, the corresponding Bragg wavelength shift for the unetched reference Bragg grating is shown in red, where dλref/dT = 10 pm/°C.
case a covalent bond was formed and the measurement made (300 MHz, δ = 4.50 [t, 6H, CH2OH], 5.45[d, 6H, CHOH], 5.53[d,
after replacing the reagent solution with a standardised ethanol 6H, CHOH]).31 This broadening corresponds to the displacement
reference. In contrast, the extent of α-CD liberated from the of solvent from the macrocyclic cavity and the formation of an
planar surface is dependent on both the sterically-limited intramolecular hydrogen-bonded structure. Subsequent re-
density of binding sites and the photostationary state of the sharpening of these peaks was observed upon exposure to UV
azobenzene-functionalised surface. Upon disassembly of the light at 365 nm wavelength (Figure S3, ESI). Complexation with
complex, released α-CD will be in diffusion-limited equilibrium α-CD was found to have little effect on the population of the
with the surrounding solution and correspondingly will still photostationary state, with the cis:trans ratio calculated to be
contribute to the effective refractive index measured by the 63:37 in solution (Figure S2, ESI). Similarly, it was found that the
Bragg grating through a near-surface increase in concentration; presence of α-CD did not perturb the absorption spectrum of
3
however, as the evanescent component of the optical mode of nor alter the rate of photoisomerisation in solution compared
the waveguide decays exponentially away from the surface such to the free system, consistent with the displacement of high
small displacements can have a disproportionate effect.
Azobenzene-functionalised polymer films are known to
energy water from the cavity driving complex formation.52
Figure 4a illustrates the divergence of the Bragg wavelength,
exhibit
a measurable change in refractive index upon δ(∆λB), for the α-CD/trans-azobenzene complex and cis-
photoisomerisation,47,48 attributed to a change in bulk matrix azobenzene surfaces, upon increasing the α-CD concentration
density upon switching between the rod-like trans-azobenzene from 330 nM to 50.0 mM. As the concentration of α-CD
and the bent cis-isomer.49 As such a control experiment in the increases, the proportion of the α-CD/azobenzene complex on
absence of α-CD was performed; it was found that when limited the surface increases, further differentiating the refractive
to a single monolayer upon the Bragg grating surface, the index of the two states. While no switching effect was observed
effects of photoisomerisation of the azobenzene moiety were when immersed in de-ionised water alone (Figure S7, ESI), for
not detected in either water (nD = 1.33), or in ethanol (1.36) low concentrations of α-CD a trend towards a 4 pm Bragg
where the sensitivity of the refractometer is amplified by the wavelength differential was observed when plotted
higher refractive index of the solvent (Figure 2c). We logarithmically, implying abstraction of cyclodextrin from
hypothesise that when limited to a discrete monolayer, the solution until an equilibrium with the inclusion complex was
molecular reconfiguration upon isomerisation of azobenzene reached. The continued increase in δ(∆λB) observed at higher
gives rise to a small change in film thickness,50,51 but the concentrations is attributed to the combined effect of dn/dc of
refractive index contrast for the corresponding small the α-CD solution53 and the non-linear sensitivity over large
displacement/ingress by solvent at the photo-stationary state is changes in analyte refractive index (dλB/dnanal, plotted in Figure
not significant enough to be observed by the Bragg grating 2c). As discussed further in the Supporting Information, the
refractometer under the experimental conditions employed.
combined effect is that the sensitivity to changes in surface-
The formation of the α-CD/azobenzene complex was localised refractive index increases with rising α-CD
confirmed in solution by 1H NMR spectroscopy in d6-DMSO concentration (Figure S8, ESI). The measured δ(∆λB) was
where, upon mixing with an equimolar solution of 4- converted to the change in analyte refractive index, δ(∆nanal),
phenylazophenoxyacetic acid (
3), broadening of the α-CD peaks using the calculated sensitivity at each measured concentration
was selectively observed for hydroxyl-bearing carbon atoms (Figure 4b). This showed that the rate of increase of δ(∆nanal) is
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
Journal of Materials Chemistry C
Page 6 of 9
ARTICLE
Journal Name
slower than the rate of complex formation. This trend is
View Article Online
47
consistent with previous polymer-boundDOIa: 1n0d.10s3u9r/fCa5cTeC-b03o7u7n4Cd
absorption studies (Figure S6, ESI). However, with a 330 nM α-
CD solution the half-time for assembly doubled, suggesting that
at this concentration and below the kinetics of host-guest
complex formation dominate.
The larger β-CD has also been reported to form an inclusion
complex with azobenzene.45 Despite issues of aqueous
solubility above 15 mM, β-CD complex formation was similarly
observed, however the magnitude of the Bragg wavelength
shift upon dynamic formation of the complex was almost three
times lower than for the equivalent α-CD solution; for
comparison δ(ΔλB) = 5 (± 1) pm for 10 mM β-CD. With the
greater size mismatch between the azobenzene on the surface
and β-CD, complex formation is less favourable reducing the
relative concentration of the complexed azobenzene on the
surface. The effect of this is similar to lowering the overall
concentration in that it reduces the surface-localised refractive
index difference between the assembled and disassembled
surfaces. Indeed this trend is seen in the literature, with the
solution-phase association constant, Ka(α-CD) having been
reported as 2000 M-1 with trans-azobenzene, but only 770 M-1
for β-CD.32 This observation also extends to the much larger γ-
CD, where photoisomerisation of the azobenzene-
functionalised surface resulted in
a Bragg wavelength
differential of only 6 (± 1) pm in the presence of a 25 mM γ-CD,
with more dilute solutions hard to resolve.
4. Conclusions
In summary, the dynamic assembly of the photo-switchable
inclusion complex between an azobenzene-functionalised
surface and α-CD has been successfully tracked in real-time via
direct measurement of surface-localised refractive index. The
refractive index differential between the two states was found
to be dependent on both the concentration and size of the
Fig. 4 (a) The average Bragg wavelength differential, δ(∆λB), between the α-
CD/trans-azobenzene complex and cis-azobenzene surfaces, as a function of α-
cyclodextrin concentration, plotted on a logarithmic x-axis. This average was
calculated from the independent, simultaneous measurement of three Bragg
gratings in thermal equilibrium over three light cycles, with the error bars
representing the standard error. (b) The difference in analyte refractive index,
δ(∆nanal), between the α-CD/trans-azobenzene complex and cis-azobenzene
surfaces, after correction for the sensitivity change arising from dn/dc of aqueous
α-CD, plotted on linear axes. Dashed lines are included as a guide for the eye only.
tending towards zero at the higher concentrations investigated. cyclodextrin, with α-CD being found to offer the largest
The gradient is estimated to be 9 x10-7 RIU/mM-1 between 40 to response upon complexation. The magnitude of the surface-
50 mM, less than the uncertainty in the refractive index localised refractive index shift, when measured in situ and in
measurement. As such, it is expected that any further raise in dynamic equilibrium with the surrounding solution, was an
concentration would not give rise to a measurable increase, order of magnitude smaller than for the deposition of the
indicating saturation of the surface binding sites. It should be covalently-attached azobenzene monolayer. This measurement
noted that the need to correct for dn/dc can be avoided by was made possible by employing a high fidelity Bragg grating
switching to a reference solvent or buffer within the flow cell, sensor in conjunction with excellent physical referencing, in
as exemplified here during covalent monolayer deposition.
However in the context of measuring binding at
particular the unique application of optical polarisation to
enable high resolution temperature referencing.
a
supramolecular surface, this requires a sufficiently slow
dissociation constant for disassembly to be trackable.38
While the absolute sensitivity limit to changes in refractive
index is comparable to the state-of-the-art for other types of
Dissociation of the surface-bound complex is driven by a integrated refractometers, such as SPR, the avoidance of bulk
perturbation of the equilibrium from the trans-azobenzene optics through the use of an optical fibre interconnect, the
guest to the less favoured cis-isomer within this dynamic ability to self-reference in situ against physical effects and the
system, as evidenced by the average dissociation half-life time use of an interrogation wavelength that does not interact with
measured to be independent of the α-CD concentration (t1/2
=
the chemistry under investigation are all significant advantages.
32 ( 6) s under the illumination conditions of the experiment; Further, the ability to measure the absolute refractive index
Figure S9, ESI). Similarly, the association rate was found to be allows for continued measurement during significant changes in
concentration independent at higher concentrations of α-CD experimental conditions (e.g. changes in solvent) or between
with t1/2 = 74 ( 6) s, indicating that photoisomerisation is experiments not possible with ‘fringe counting’ based
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 9
Journal of Materials Chemistry C
Please do not adjust margins
Journal Name
ARTICLE
Langmuir, 2013, 29, 14101–14107.
19. O. Crespo-Biel, B. Dordi, D. N. Reinhoudt, and J. Huskens, J. Am.
Chem. Soc., 2005, 127, 7594–7600.
20. P. Sun, Y. Jiang, G. Xie, X. Du, and J. Hu, Sensors Actuators B
Chem., 2009, 141, 104–108.
approaches used in interferometric systems. Future studies,
when not rate-limited by photo-excitation of the surface-bound
guest or the presence of a photostationary state, will look to
employ the methodology used in SPR to quantify and compare
the degree of binding and the kinetics of supramolecular
chemistry on a surface with solution-based analogues.
View Article Online
DOI: 10.1039/C5TC03774C
21. M. Brutschy, M. W. Schneider, M. Mastalerz, and S. R.
Waldvogel, Chem. Commun., 2013, 49, 8398–8400.
22. X. Fan, I. M. White, S. I. Shopova, H. Zhu, J. D. Suter, and Y. Sun,
Anal. Chim. Acta, 2008, 620, 8–26.
23. D. Bhatta, E. Stadden, E. Hashem, I. J. G. Sparrow, and G. D.
Emmerson, Sensors Actuators B Chem., 2010, 149, 233–238.
24. C. Ciminelli, C. M. Campanella, F. Dell’Olio, C. E. Campanella,
and M. N. Armenise, Prog. Quantum Electron., 2013, 37, 51–
107.
25. M. Li, S. K. Cushing, and N. Wu, Analyst, 2014, 140, 386–406.
26. M. Kutscher, M. Rosenberger, B. Schmauss, L. Meinel, U.
Lorenz, K. Ohlsen, R. Hellmann, and O. Germershaus, J.
Biophotonics, 2015, DOI: 10.1002/jbio.201500178.
27. H. Murakami, A. Kawabuchi, R. Matsumoto, T. Ido, and N.
Nakashima, J. Am. Chem. Soc., 2005, 127, 15891–15899.
28. I. Willner, V. Pardo-Yissar, E. Katz, and K. T. Ranjit, J. Electroanal.
Chem., 2001, 497, 172–177.
29. Ipsita A. Banerjee, L. Yu, and H. Matsui, J. Am. Chem. Soc., 2003,
125, 9542–9543.
30. Y.-L. Zhao and F. Stoddart, Langmuir, 2009, 25, 8442–8446.
31. S. Tamesue, Y. Takashima, H. Yamaguchi, S. Shinkai, and A.
Harada, Angew. Chem., 2010, 49, 7461–7464.
32. H. Yamaguchi, Y. Kobayashi, R. Kobayashi, Y. Takashima, A.
Hashidzume, and A. Harada, Nat. Commun., 2011, 3, 603.
33. M. Girschikofsky, M. Rosenberger, S. Belle, M. Brutschy, S. R.
Waldvogel, and R. Hellmann, Anal. Chim. Acta, 2013, 791, 51–
59.
34. G. D. Emmerson, S. P. Watts, C. B. E. Gawith, V. Albanis, M.
Ibsen, R. B. Williams, and P. G. R. Smith, Electron. Lett., 2002,
38, 1531–1532.
The compatibility of integrated optical Bragg refractometers
with microfluidics, combined with the ability to fabricate
multiple distinct gratings within a single waveguide, offers the
potential for simultaneous sensor measurements, self-
referenced against both the chemical environment and physical
phenomena. Applying this ability to directly probe surface-
based supramolecular interactions in situ and in real-time, via
near-field refractive index measurement offers a valuable new
tool in the understanding of such complex dynamic
supramolecular systems.
Acknowledgements
This work was supported by the UK Engineering Physical
Sciences Research Council PhD Plus Fellowship for RMP (EPSRC:
EP/P505739/1). DJW acknowledges EPSRC (EPSRC DTG:
EP/P505119/1) and the European Regional Development Fund
(ERDF) for co-financing the ISCE-Chem project (No. 4061)
through the INTERREG IV A France (Channel) - England cross-
border cooperation programme.
References
1. J.-M. Lehn, Proc. Natl. Acad. Sci., 2002, 99, 4763–4768.
2. F. Tian, D. Z. Jiao, F. Biedermann, and O. A. Scherman, Nat.
Commun., 2012, 3, 1207.
3. M. von Delius, E. M. Geertsema, and D. A. Leigh, Nat. Chem.,
2010, 2, 96–101.
4. E. R. Kay and D. A. Leigh, Angew. Chem., 2015, 54, 10080–
10088.
5. S. Erbas-Cakmak, D. A. Leigh, C. T. McTernan, and A. L.
Nussbaumer, Chem. Rev., 2015, 115, 10081–10206.
6. D. N. Reinhoudt and M. Crego-Calama, Science, 2002, 295,
2403–2407.
35. C. Holmes, J. C. Gates, L. G. Carpenter, H. L. Rogers, R. M.
Parker, P. A. Cooper, F. R. M. Adikan, C. B. E. Gawith, and P. G.
R. Smith, Meas. Sci. Technol., 2015, 26, 112001.
36. R. M. Parker, J. C. Gates, M. C. Grossel, and P. G. R. Smith, Appl.
Phys. Lett., 2009, 95, 173306.
37. R. M. Parker, J. C. Gates, D. J. Wales, P. G. R. Smith, and M. C.
Grossel, Lab Chip, 2013, 13, 377–385.
7. G. R. Desiraju, J. Chem. Sci., 2010, 122, 667–675.
8. M. Cavallini, F. Biscarini, S. Léon, F. Zerbetto, G. Bottari, and D.
A. Leigh, Science, 2003, 299, 531.
9. A. G. Slater, L. M. A. Perdigão, P. H. Beton, and N. R.
Champness, Acc. Chem. Res., 2014, 47, 3417–3427.
10. J. A. A. Elemans, S. Lei, and S. De Feyter, Angew. Chem., 2009,
48, 7298–7332.
38. R. M. Parker, D. J. Wales, J. C. Gates, J. G. Frey, P. G. R. Smith,
and M. C. Grossel, Analyst, 2014, 139, 2774–2782.
39. R. M. Parker, J. C. Gates, M. C. Grossel, and P. G. R. Smith,
Sensors Actuators, B, 2010, 145, 428–432.
40. A. Ault, Techniques and experiments for organic chemistry,
University Science Books, 4th edn., 1976.
41. M. Odabasoglu, G. Turgut, and H. Kocaokutgen, Phosphorus,
Sulfur Silicon Relat. Elem., 1999, 152, 27–34.
11. A. Ulman, Chem. Rev., 1996, 1533–1554.
12. Y. Liu, A. H. Flood, P. A. Bonvallet, S. A. Vignon, B. H. Northrop,
H.-R. Tseng, J. O. Jeppesen, T. J. Huang, B. Brough, M. Baller, S.
Magonov, S. D. Solares, W. A. Goddard, C.-M. Ho, and J. F.
Stoddart, J. Am. Chem. Soc., 2005, 127, 9745–9759.
13. F. Zaera, Chem. Rev., 2012, 112, 2920–2986.
14. D. P. Ferris, Y.-L. Zhao, N. M. Khashab, H. A. Khatib, J. F.
Stoddart, and J. I. Zink, J. Am. Chem. Soc., 2009, 131, 1686–
1688.
15. D. Velic and G. Kohler, Chem. Phys. Lett., 2003, 371, 483–489.
16. Y. Maeda and H. Kitano, J. Phys. Chem., 1995, 99, 487–488.
17. D. G. Kurth and T. Bein, Angew. Chem., 1992, 31, 336–338.
18. D. Li, K. Ren, H. Chang, H. Wang, J. Wang, C. Chen, and J. Ji,
42. J. Kim and B. M. Novak, Macromolecules, 2004, 37, 8286–8292.
43. D. Jackson, PhD Thesis, University of Southampton, 2008.
44. K. A. Connors, Chem. Rev., 1997, 97, 1325–1358.
45. P. Bortolus and S. Monti, J. Phys. Chem., 1987, 91, 5046–5050.
46. W. Wang and M.-Z. Wang, Polym. Bull., 2007, 59, 537–544.
47. R. M. Parker, J. C. Gates, H. L. Rogers, P. G. R. Smith, and M. C.
Grossel, J. Mater. Chem., 2010, 20, 9118–9125.
48. S. H. Barley, A. Gilbert, and G. R. Mitchell, J. Mater. Chem.,
1991, 1, 481–482.
49. H. Kudo, M. Yamamoto, and T. Nishikubo, Macromolecules,
2006, 39, 1759–1765.
50. P. Ahonen, T. Laaksonen, D. J. Schiffrin, and K. Kontturi, Phys.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins

Please do not adjust margins
Journal of Materials Chemistry C
Page 8 of 9
ARTICLE
Chem. Chem. Phys., 2007, 9, 4898–4901.
Journal Name
View Article Online
51. H. Knobloch, S. Katholy, J. Hesse, H. Orendi, D. Prescher, R.
Ruhmann, and L. Brehmer, Mater. Sci. Eng. C, 1998, 5, 307–310.
52. J. Szejtli, Chem. Rev., 1998, 98, 1743–1754.
DOI: 10.1039/C5TC03774C
53. G. M. Pavlov, E. V. Korneeva, N. A. Smolina, and U. S. Schubert,
Eur. Biophys. J., 2010, 39, 371–379.
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Journal of Materials Chemistry C
Page 9 of 9
ARTICLE
Journal Name
View Article Online
DOI: 10.1039/C5TC03774C
Table of contents image:
An integrated optical Bragg grating sensor, capable of evanescently detecting small changes in refractive index, is employed to
probe the dynamic surface-localised supramolecular interaction between an azobenzene-functionalised monolayer and
cyclodextrin in solution.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
Please do not adjust margins