Reversible Trapping of Functional Molecules at Interfaces Using

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Reversible Trapping of Functional Molecules at interfaces Using Diazonium Salts Chemistry Doriane Heimburger, Sarra Gam Derouich, Philippe Decorse, Claire Mangeney, and Jean Pinson Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.6b02468 • Publication Date (Web): 02 Sep 2016 Downloaded from http://pubs.acs.org on September 7, 2016

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Reversible Trapping of Functional Molecules at Interfaces Using Diazonium Salts Chemistry Doriane Heimburger, Sarra Gam-Derouich, Philippe Decorse, Claire Mangeney,* Jean Pinson* Univ Paris Diderot, Sorbonne Paris Cité, ITODYS, UMR 7086 CNRS, 15 rue J-A de Baïf, 75205 Paris Cedex 13, France

ABSTRACT. Developing thin polymeric films for trapping, releasing, delivering and sensing molecules is important for many applications in chemistry, biotechnology and environment. Hence, a facile and scalable technique for loading specific molecules on surfaces would rapidly translate into applications. This work presents a novel method for the trapping of functional molecules at interfaces by exploiting diazonium salt chemistry. We demonstrate the efficiency of this approach by trapping two different molecules, 4-nitrobenzophenone and paracetamol, within polycarboxyphenyl layers grafted on gold and glassy carbon (GC) and by releasing them in acidic medium. The former molecule was chosen as a proof of concept for its electrochemical and spectroscopic properties and the latter one was selected as an example of a pharmaceutical molecule. Advantages of the present approach rely on the simplicity, rapidity, and efficiency of the procedure for the reversible, on demand, trapping and release of functional molecules. INTRODUCTION Tailoring the surface properties of materials is a crucial step for many applications in chemistry and biotechnology. The various strategies, which have been developed so far for

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surface modification, depend on the nature of the material (thiols or disulfides for precious metals,1 halogenosilanes, alkoxysilanes, carboxylic acids or phosphonic acids for oxides2..). As an alternative, diazonium salts have emerged these past years as a new generation of surface modifiers being able to functionalize a wide range of substrates (metals, oxides, carbon, semiconductors and polymers..).3,4 The main mechanism for the grafting reaction is a two-stage process: (i) first, the electrochemical or spontaneous reduction of the diazonium salts generates an aryl radical that binds to the surface and (ii) in a second step, due to their high reactivity, these radicals react with the first grafted layer to give nanometer to micrometer thick polyaryl layers (see Figure 1).5 Strongly attached disordered mono- or multilayers are obtained by this method, the interaction between the diazonium-derived aryl films and the surface being very stable.4 R

+ 1e-

S +

S

+

.

S

R

R

+

+

N

A-

N

S

R

.

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S

R

R

R R

R

n

Figure 1. Simplified scheme of surface functionalization and formation of polycarboxyphenyl films by reduction of diazonium salts.

In most studies, the diazonium salts have been considered as simple and efficient coupling agents between the surface and functional species. For example, they were used to attach DNA,6,7 proteins,6 calixarenes,8 polymers9,10 or nanoparticles.11,12 However, contrary to selfassembled monolayers of thiol molecules on gold, the thickness of the diazonium-derived aryl layers is difficult to control due to the reaction of radicals on the first grafted layer. In the 2 ACS Paragon Plus Environment

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perspective of using them as coupling agents, the polymerization step following the grafting of the first aryl layers was generally considered useless or in some case a significant adverse effect. In order to obtain monolayers derived from diazonium salts, various types of blocking substituents were introduced on the aryl groups of the diazonium salts, inhibiting the polymerization step.4 If a number of studies have focused on the design of perfectly controlled diazonium-derived aryl monolayers, much less research has been devoted to the large opportunities offered by the secondary polymerization step, which leads to strongly anchored polyaryl layers. For example, such layers are useful for the analytical detection and quantification13,14,15 of ions Pb(II), Cu(II), U(VI). In this work, we propose to explore the potentialities of the secondary polymerization process occurring during the functionalization of surfaces by aryl diazonium salts, to trap functional molecules inside polycarboxyphenyl layers. The proposed approach is very simple and relies on the electrochemical functionalization of the substrates from a mixture of the functional molecule and the diazonium salt. This one-step procedure for surface modification represents an original strategy to entrap and release molecules in the vicinity of a surface. Trapping of molecules on surfaces has already been achieved with Molecularly Imprinted Polymers (MIP)16,17 where functional and cross-linking monomers are co-polymerized in the presence of the target analyte (the imprint molecule), which acts as a molecular template. For example, polymerization initiators can be grafted on surfaces through diazonium chemistry and a polymer grown from this initiator by ATRP (Atom Transfer Radical Polymerization) or radical photopolymerization in the presence of the target molecule18 (quercetin, melamine,…).


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We demonstrate this approach by grafting polycarboxyphenyl layers derived from 4carboxybenzenediazonium tetrafluoroborate on gold and glassy carbon (GC),3 in the presence of two model functional molecules (Figure 2): (i) 4-nitrobenzophenone that presents interesting electrochemical and spectroscopic properties and (ii) paracetamol, which is a widespread pharmaceutical compound used as a pain reliever and a fever reducer.19 The former can be reduced while the later can be oxidized. The possibility to deliver pharmaceutical molecules from a surface is of particular interest for drug-release biomaterials. Conversely, as a result of its extensive use, paracetamol has been identified as an emerging pharmaceutical contaminant widely dispersed in the environment.20,21 The extraction and sensitive determination of paracetamol is thus important from the clinical and health viewpoints. The possibility to trap and release paracetamol in thin polymer films should therefore open up new opportunities in the fields of biomedicine and environment. O N

CH3

+

O

-

HN

O

O

OH 4-nitrobenzophenone

Paracetamol

Figure 2. Structure of the investigated molecules.

Experimental section Chemicals. Paracetamol and 4-nitrobenzophenone were obtained from Sigma-Aldrich. 4carboxyphenyldiazonium tetrafluoroborate (+N2-C6H4-C(=O)OH, BF4-) was prepared in aqueous solution from 4-aminobenzoic acid and sodium nitrite.22 White solid; 1H NMR 4 ACS Paragon Plus Environment

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(DMSOd6, Bruker 400 Mhz) δ ppm: 8.77 (d, 2H, J = 8 Hz), 8.42 (d, 2H, J = 8Hz) , IRATR: N≡N+ 2301 cm-1 , C=O 1725 cm-1; aromatic ring 1612, 1511 cm-1. Electrochemical Measurements. Electrodes for cyclic voltammetry were Au wires (d= 1 mm) and GC carbon rods (Tokai , Japan, d = 2 mm, A = 0.027 cm2, calculated from the voltammogram of ferrocene methanol , c = 1 mM) imbedded in epoxy resin. Gold and carbon electrodes were chosen for 4-nitrobenzophenone and paracetamol, respectively, as they gave the best defined voltammograms. They were polished with different grades of polishing paper and finally with a 0.3 µm alumina slurry on a polishing cloth (DP-Nap, Struers, Denmark) using a Presi Mecatech 234 polishing machine. After being polished, the electrodes were rinsed with Milli-Q water and sonicated for 10 min in ethanol to avoid organic contaminants. Gold-coated silicon wafers (1×1cm2, Sigma Aldrich, 100 nm coating) were cleaned with concentrated H2SO4 at room temperature, and rinsed under sonication for 5 min in Milli-Q water, 5mn in acetone and 5mn in absolute ethanol. Before modification, the plates were dried in a stream of nitrogen. Cyclic Voltammetry experiments were performed with a potentiostat Versastat 4 potentiostat/galvanostat/EIS from Princeton Applied Research analyzer with VersaStudio software. Experiments were carried out in ACN + 0.1M NBu4BF4 or pH7 buffer solutions deoxygenated with argon for the preparation of the films. All potentials were measured versus the SCE electrode. The films were prepared in ACN + 0.1 M NBu4BF4 + 0.01 M carboxybenzenediazonium tetrafluoroborate, 0.01M 4-nitrobenzophenone or paracetamol by scanning (100 scans) the potential from 0 V to -0.5 V/SCE for 4-nitrobenzophenone and from 0 to -1 V/SCE for paracetamol, the scan rate was 50 mV s-1. In the former case the potential is limited to -0.5


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V/SCE to prevent the reduction of 4-nitrobenzophenone. When different concentrations are used, they are indicated in the text.

IR Spectra. The IRRAS and ATR spectra of modified plates were recorded using a purged (low CO2, dry air) Jasco FT/IR-6100 Fourier Transform InfraRed Spectrometer equipped with MCT (mercury-cadmium-telluride) detector. For each spectrum, 1000 scans were accumulated with a spectral resolution of 4 cm-1. The background recorded before each spectrum was that of a clean substrate. ATR spectra were recorded with a germanium ATR accessory (Jasco ATR PR0470-H). XPS Spectra. X-ray photoelectron spectra were recorded using a Thermo VG Scientific ESCALAB 250 system fitted with a micro-focused, monochromatic Al Kα X-ray source (1486.6 eV) and a magnetic lens, which increases the electron acceptance angle and hence the sensitivity. The pass energy was set at 100, 40 or 15 eV (for high resolution C1s spectra) for the survey and the narrow regions, respectively. The Avantage Software, version 4.67, was used for digital acquisition and data processing. The spectra were calibrated against C1s set at 285 eV. Ellipsometry. The thicknesses of the films on Au were measured with a Sentech SE400 mono wavelength ellipsometer. For Au, the following values were taken as refractive indexes, ns, and dispersion coefficients, ks: ns = 0.185, ks = 3.399. These values were measured on clean surfaces before grafting, and the film thicknesses were deduced from the same plates after modification, taking ns = 1.46 and ks = 0 for the organic layer.

Results and Discussion


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Preparation of polycarboxyphenyl layers trapping functional molecules The surface modification procedure proposed here is very simple as it consists in introducing the substrate, the functional molecule and the diazonium salt in the same solution containing the electrolyte and to perform the electrochemical reduction of the diazonium salt by repetitive cyclic voltammetry. We first examined the cyclic voltammetry of 4carboxybenzenediazonium alone and characterized the film that forms on the electrode. The cyclic voltammetry of 4-carboxybenzenediazonium (in ACN + 0.1M NBu4BF4) presents an irreversible reduction peak located at Ep = - 0.16 V/SCE on a GC electrode (with a prewave often observed with diazonium salts on GC electrodes23) that decreases to nearly zero upon repetitive scanning due to the blocking of the electrode by the generated polycarboxyphenyl film (Figure S1). After 100 successive cyclic voltammograms (scan rate: v = 0.05 Vs-1, scan range 0 to -1.0 V/SCE) in ACN + 0.1M NBu4BF4 + 0.01 M 4-carboxybenzenediazonium, a polycarboxyphenyl film was grafted on the electrode. The voltammogram of this film does not present any signal in the reduction range of 4-nitrobenzophenone in ACN or in the oxidation range of paracetamol at pH 7 (Figure S2) which could hamper the detection of these two molecules. The polycarboxyphenyl film formed on an Au plate was characterized by IRRAS; the spectrum of the film presents characteristic bands: C=O at 1710 cm-1 and an aromatic ring at 1603 cm-1(Figure 3), similar to that of benzoic acid: C=O at 1684 cm-1 and aromatic ring at 1602 cm-1, demonstrating the success of the grafting reaction.


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a.u.

Abs

C=O aromatic

a 0 2000

b 1800 1600 Wavenumber [cm-1]

1400

Figure 3. IR spectra of a) a gold plate modified by polycarboxyphenyl film (IRRAS) and b) benzoic acid (ATR). Normalized spectra, arbitrary absorbance units.

Then polycarboxyphenyl films imbedding 4-nitrobenzophenone or paracetamol were prepared on GC and Au electrodes respectively, by reducing 4-carboxybenzenediazonium in the presence of either of the two molecules as indicated in the experimental section. When these modified electrodes are transferred to an ACN (for 4-nitrobenzophenone) or pH7 solution (for paracetamol, in order to roughly mimic biological or environmental conditions), it is possible to observe the signature of both entrapped molecules (Figure 4). 4-Nitrobenzophenone can be detected (Figure 4Ab in ACN) inside the polycarboxyphenyl film through a broad irreversible voltammetric reduction peak at Ep = -0.80 V/SCE and paracetamol through an irreversible anodic peak located at Epa ~ + 0.43 V/SCE (Figure 4Bb) in pH 7 buffer; both potentials are very close to that observed in solution. Indeed, the cyclic voltammetry of 4nitrobenzophenone recorded in acetonitrile (ACN) containing NBu4BF4 (0.1 M) and benzoic acid (0.1 M) (to mimic the environment in the polycarboxyphenyl film) is characterized by a two electrons irreversible peak (by comparison of ip/cv0.5 with the reversible wave of ferrocene) located at Ep = -0.92 V/SCE (Figure 4 Aa).24,25 The cyclic voltammetry of paracetamol26 in aqueous solution (c = 1 mM, pH 7 buffer) presents a partly reversible two electrons oxidation peak at Ep = + 0.38 V/SCE (Figure 4Ba).


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10

0.2

Aa

-0.2

I(µA)

-10

I (µA)

Ac

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Ba 60

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I (µA)

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I (µA)

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0,2

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V/SCE

V/SCE

Figure 4. Cyclic voltammetry on A) a gold electrode (d = 1mm) in ACN + 0.1M NBu4BF4 and B) a GC electrode (d = 2 mm) in a pH 7 buffer. Aa) 4-nitrobenzophenone (c = 10-3 M) in ACN +0.1M NBu4BF4 +0.1 M benzoic acid; Ab) 4-nitrobenzophenone inside the polycarboxyphenyl film in ACN +0.1M NBu4BF4; Ac) the same film after extraction of the trapped molecule in acetic acid; Ba) paracetamol in pH 7 solution (c =10-3 M).; Bb) paracetamol inside the polycarboxyphenyl film; Bc) the same film after extraction of the paracetamol in acetic acid. v = 100 mVs-1, reference SCE.

Interestingly, the polycarboxyphenyl films prepared in the absence of any functional molecules appeared to be also very efficient to trap paracetamol. Indeed, when the asprepared films were dipped in a 0.1M solution of paracetamol in pH 7 buffer, the voltammetric peak recorded after 30 min was equivalent to that obtained after reducing the diazonium salt, in the presence of paracetamol. 9 ACS Paragon Plus Environment

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Characterization of the films with embedded functional molecules The surface projected concentration of molecules in the polycarboxyphenyl film Г (mol cm-2) was estimated by integration of the voltammograms (see Table 1). Table

1.

Surface concentration

of

the

functional

molecules entrapped

in

the

polycarboxyphenyl film. Molecule

Electrode Concentration Γ in mol Concentration in the

cm-2

of the reloading cm-2

Solution (M)

after

solution

after reloadinga)

synthesis 4-

Γ in mol

Au

0.01

0.3 10-10

0.01

0.7 10-10

GC

0.01

0.7 10-10

0.01

8.1 10-10

0.1

3.3 10-10

0.1

13.2 10-10

0.01

2.0 10-10

nitrobenzophenone

Paracetamol

a) The molecule was removed from the film and reloaded from a solution of the functional molecules (see text). Indeed, the area under the voltammetric peak corresponds to the total charge Q = 2 F Γ A, where 2 is the number of electrons transferred during the reduction of 4-nitrobenzophenone or the oxidation of paracetamol, F is the Faraday constant and A is the surface of the electrode in cm2. The magnitude of the projected surface concentration (Γ) of the molecules imbedded in the polycarboxyphenyl film ranges from 0.3 to 13.2 10-10 mol cm-2. It is noteworthy that Γ is higher after reloading in the same solution than directly after the synthesis and increases with the concentration of the reloading solution.


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The presence of the trapped molecules in the film was confirmed by IR spectroscopy. Figure 5 presents the spectrum of 4-nitrobenzophenone in the polycarboxyphenyl film (prepared from 0.05 M 4-nitrobenzophenone) ; there is an excellent match between the characteristic vibrations of 4-nitrobenzophenone (C=O band at 1649 cm-1, aromatic vibrations at 1592 cm-1 and two asymmetric and symmetric NO2 bands at 1511 and 1354 cm-1), and the spectrum of the film (C=O bands at 1649 cm-1 and as and s NO2 band at 1500 and 1348 cm1

, in addition to the C=O band of the polycarboxyphenyl film). The spectrum of paracetamol

in the polycarboxyphenyl film (prepared from a 0.01M solution of paracetamol, Figure 6) displays, in addition to the C=O band of the polycarboxyphenyl film, the peaks pertaining to paracetamol at 1652 (-C=O), 1611(-aryl) , 1557 (-NH) cm-1.27 These spectra indicate the imbedding of 4-nitrobenzophenone and paracetamol in the polymer.

NO2

NO2

C=O (c)

Abs

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C=O (b)

(a)

1800

1700

1600

1500

1400

1300

1200

-1

Wavenumbers (cm )

Figure 5. IR spectra of a) a gold surface with a grafted polycarboxyphenyl film (IRRAS), b) 4-nitrobenzophenone as crystals (ATR) and c) trapped inside the film (IRRAS). Normalized spectra, arbitrary absorbance units.


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(c)

Abs

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(b) C=O Ar N-H

(a)

1800

1700

1600

1500

1400 -1

Wavenumbers (cm )

Figure 6. IR spectra of a) the polycarboxyphenyl film (IRRAS). b) paracetamol (ATR) c) paracetamol inside the polycarboxyphenyl film on a gold surface (IRRAS). Normalized spectra, arbitrary absorbance units.

The dry-state thickness of the film was determined using ellipsometry on Au surfaces. The reference sample, corresponding to the polycarboxyphenyl film synthesized in the absence of any functional molecules, exhibits a thickness of th = 3.6 ± 0.3 nm, confirming the polymeric character of the layer (a monolayer would give a thickness of around 0.7-0.8 nm). In the presence of 4-nitrobenzophenone and paracetamol (c = 0.01M), the film thickness increases to th= 5.1 ± 0.4 nm and 7.3 ± 1.5 nm, respectively. The inclusion of entrapped molecules inside the polycarboxyphenyl layer thus appears to induce a large conformational change of the polymeric carboxylic chains and the intercalation of the molecules between them. Interestingly, after extraction of paracetamol, the film thickness decreases to 1.6 ± 1.0 nm, indicating a collapse of the polymer chains at the surface. From these results, it appears that the polycarboxyphenyl chains tethered on the surface undergo a change of conformation in response to the presence or absence of paracetamol, thus behaving as stimuli-responsive polymers. The compactness of the films (with or without paracetamol) was studied using two redox probes: (i) ferrocenemethanol, a small neutral molecule, which oxidation proceeds via an 12 ACS Paragon Plus Environment

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outer sphere one-electron transfer (i.e. the electron transfer occurs even if the molecule is not in direct contact with the electrode) and (ii) ferrocyanide (Fe(CN)63-/4-), a negatively charged ion, oxidized along an inner sphere process (the molecule must contact the electrode for the electron transfer to occur). Interestingly, the electroactive behavior of these two redox probes on the polycarboxyphenyl-coated electrodes is very different (see Figure 7).

(A) 40

Current (µ A)

(b) on polycarboxyphenyl film

(c) on polycarboxyphenyl film containing paracetamol

20

0 0,0

0,1

0,2

0,3

0,4

Potential (V) -20

(a) bare electrode -40

(B)

(d) on extracted polycarboxyphenyl film

Current (µ A)

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300

(a) bare electrode (c) on polycarboxyphenyl film containing paracetamol

200

(d) on extracted polycarboxyphenyl film

100

0 -0,2

0,0

0,2

0,4

0,6

Potential (V) -100 (b) on polycarboxyphenyl film -200

-300

Figure 7. Redox probe experiments in pH7 buffered solution on a GC electrode. A) ferrocene/ferriciniummethanol. B) Potassium Ferro/ferricyanide as redox probes. Ferrocenemethanol and potassium ferrocyanide in solution (c= 5 mM): Aa and Ba) on an unmodified GC electrode; Ab and Bb) on the polycarboxyphenyl films; Ac and Bc) on the polycarboxyphenyl film trapping paracetamol; Ad and Bd) on the extracted polycarboxyphenyl film.

.

Indeed, the reversible voltammogram of ferrocenemethanol/ferrocenemethanol + (c = 5 mM) on the bare electrode (Figure 7Aa) is nearly unaffected by the grafting of the polycarboxyphenyl layers on the electrode (Figure 7Ab), and by trapping (Figure 7Ac) or releasing (Figure 7Ad) paracetamol, the current of the oxidation peak remaining constant, close to ipa= 30 µA. In contrast, the reversible voltammogram of ferro/ferricyanide (c = 5 mM) observed on a bare electrode (Figure 7Ba), is completely inhibited after coating by the polycarboxyphenyl layer (Figure 7Bb), indicating that the ion cannot reach the electrode. This can be explained by the presence of a rather compact layer on the electrode. On the 13 ACS Paragon Plus Environment

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polycarboxyphenyl films embedding paracetamol (Figure 7Bc), a sigmoid curve is observed. This peculiar shape suggests that the electrochemical response originates from small pinholes within the film. Indeed, in a film containing small and widely spaced pinholes (relative to the diffusion layer thickness) these pinholes act as a collection of non-overlapping ultramicroelectrodes and a pure S-shaped voltammogram is expected.28,29After extraction of paracetamol the reversible voltammogram of the ferro/ferricyanide is restored albeit with a lower intensity (Figure 7Bd). The trapping of paracetamol within the film during its formation leads therefore to a porous film with opened pinholes, in agreement with the large swelling effect observed previously due to the change of steric conformation of the polymeric carboxylic chains. This behavior is exacerbated after extraction of the trapped molecules as can be seen on the voltamogram exhibiting peak potential of ferro/ferricyanide similar to that observed on an unmodified electrode, the oxidation peak current reaching almost 70% of the initial value. The porosity of the layer is then very high. These experiments give a rather clear image of the structure of the polycarboxyphenyl film: relatively compact, it becomes porous due to the deformations induced by the imbedding of paracetamol. When this functional molecule is removed, the film is completely opened. Note that unlike polymethylmethacrylate films,30 constituted of sp3 carbons and therefore highly flexible, polycarboxyphenyl films can only change their conformation by rotation around C(sp2)-C(sp2) bonds which breaks the π- π conjugation between the aromatic cycles.


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The number of paracetamol molecules per carboxyphenyl groups inside the films was estimated using XPS by comparing Au plates grafted with polycarboxyphenyl layers with and without paracetamol (the film containing paracetamol was prepared from a 0.1M paracetamol solution). The high resolution C1s spectra of the films revealed the presence of several

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photoemission peaks corresponding to the various groups present in the layers (see Figure 8).

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C-O, C-N N-C=O O-C=O shake-up

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Binding Energy /eV

Figure 8. C1s high resolution XPS spectra of (a) a bare Au electrode; (b) the polycarboxyphenyl film; (c) the film with embedded paracetamol. The Table reports the relative area of the various components in the C1s high resolution spectra.

For comparison, the C1s signal of a reference bare Au plate originating from adventitious contamination was also recorded (Figure 8a). The spectrum (Figure 8b) of polycarboxyphenyl layers displays the characteristic signal of aromatic rings with C-C/C=C peak at ca. 285 eV and a small component at ca. 291 eV due to the π→π* shake-up satellite. The peak at 286.6 15 ACS Paragon Plus Environment

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eV is due to C-O photoelectrons while the one at 289 eV corresponds to the O-C=O carboxyl groups. The presence of paracetamol within the films is clearly detected in Figure 8c, through the net increase of the C-O/C-N peak at 286.6 eV and the appearance of a new component at 287.5 eV assigned to the N-C=O amide moieties of paracetamol. The area ratio between the component at 289 eV (Icarboxyl) and the component at 287.5 eV (Iamide) was used to estimate the ratio of paracetamol per carboxyphenyl groups. Icarboxyl/Iamide = 2.3, indicating that one paracetamol molecule is trapped by approximately 2 carboxyphenyl groups. The structure of the film could also be inferred from the examination of co-crystals obtained with paracetamol, which would provide an ordered version of the disordered polymer containing paracetamol. Unfortunately under our hands, benzoic acid and paracetamol only gave separate crystals. Among the different co-crystals obtained from paracetamol31 in the literature, a co-crystal was obtained in a 2/1 molar ratio of paracetamol to citric acid. This is in agreement with the value obtained from XPS on the polycarboxyphenyl films trapping paracetamol. The asymmetric unit of the crystal contains two paracetamol molecules hydrogen-bonded to the citric acid; one of these acts as a phenolic-OH hydrogen bond donor to the carbonyl of a carboxylic acid arm of citric acid. In contrast, the other phenolic-OH acts as a hydrogen bond acceptor from the quaternary C–OH of citric acid.32

Trapping/Release capacity of the polycarboxyphenyl films The functional molecules trapped within the polycarboxyphenyl layer can be entirely extracted from the film by stirring in a 50% v/v acetic acid/water solution for 30 min, as shown by the voltammograms of Figure 4Ac and 4Bc. With more dilute acetic acid solutions or at pH7 extraction is not complete. This pH and solvent dependent behavior can be explained as follows: with 4-nitrobenzophenone, the films are prepared and maintained in ACN. The carboxylic functions should remain protonated (pKa of benzoic acid33 in ACN:


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21.5 and that of ACN 28.934) and the molecule should therefore be retained inside the film through H bonds between the nitro and carbonyl group of 4-nitrobenzophenone and the carboxylic functions of benzoic acid.35 On the contrary, the electrostatic interactions between the carbonyl goup (Cδ+=Oδ−) and the nitro group (Nδ+-Oδ−) should be repulsive. Therefore, ACN cannot extract 4-nitrobenzophenone as it is both a weak hydrogen bond donor and acceptor,36 but the acetic acid/water solvent is a good hydrogen bonding solvent that easily extracts the molecule. With paracetamol, the films are prepared in water at pH 7, where the carboxylic groups are deprotonated. It is noteworthy that incubation of the films containing paracetamol in a buffer solution at pH7 does not lead to the release of the molecules even after one night in the solution. At this pH value, paracetamol (pKa = 9.5) remains protonated, and the interactions between the film and paracetamol should be of electrostatic nature between the negatively charged carboxylates and the atoms of paracetamol bearing partial positive charges: C-N (0.543 e-), C=O (0.485 e-), O-H (0.485 e-) and N-H (0.286 e-).31 As the pH decreases, the carboxylic groups protonate and the electrostatic interactions formed between the polycarboxyphenyl layers and the functional molecules break, leading to the release of 4nitrobenzophenone and paracetamol at pH 4. The reversibility of the trapping/release capacity of the films was evaluated by incubating the extracted film with increasing concentrations of the functional molecules in solution, for 1 hour. The experiments were performed by trapping 4-nitrobenzophenone or paracetamol from 10-10 or 10-9 M solutions, releasing the molecules in 50:50 acetic acid water, retrapping from a solution 10 time more concentrated, releasing and so on, up to a 10-1 or 10-2 M solution. This shows that the trapping/releasing process is highly reversible as it can be performed at least eight times. After releasing the molecules, the Differential Pulse Voltammetry curves (DPV) for 4-nitrobenzophenone (Figure 9A) and the cyclic voltammograms for paracetamol 17 ACS Paragon Plus Environment

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(Figure 9B) (the DPV curve of paracetamol is poorly defined) were recorded from 10-10 to 101

M (only some of them are presented in Figure 9). They show well defined waves, down to a

10-10 M concentration.

Figure 9. A) Differential pulse voltammetry and B) Cyclic voltammetry recorded on the extracted polyarylcoated electrodes after incubation in aqueous solutions containing decreasing concentrations of A: 4nitrobenzophenone at a) 10-1 M, b) 10-9 M, c) 10-10 M in ACN + 0.1M NBu4BF4 and B: paracetamol, at a) 10-2 M, b) 10-4 M, c) 10-9 M in pH 7 buffer.

The peak current increases progressively with the concentration of paracetamol and 4nitrobenzophenone. From the height of the voltammograms as a function of the concentration of paracetamol, one can obtain the curve of Figure 10. This indicates an efficient re-trapping of the molecules within the extracted polycarboxyphenyl layers.


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50 40

Ip (µA)

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30 20 10 0 -10

-9

-8

-7

-6

-5

log (C)

-4

-3

-2

-1

Figure 10. Variation of the peak current Ip of the voltammogram recorded on the extracted polycarboxyphenyl films during retrapping of paracetamol as a function of the concentration of the solution. Modified GC electrode, v = 100 mV s-1, reference SCE. The curve is only a guide for the eye.

We also examined the selectivity of the films. A modified GC electrode was prepared, as in the experimental section by grafting 4-carboxyphenyldiazonium tetrafluoroborate in the presence of paracetamol (c = 10 mM). After extraction of paracetamol, the electrode was dipped for one hour in a 10 mM solution of 4-nitrobenzophenone in ACN + 0.1 M NBu4BF4 and rinsed. The voltammogram recorded in ACN + 0.1M NBu4BF4 with this modified electrode does not show any signal at the potential of 4-nitrobenzophenone (Figure S3). Conversely two GC electrodes modified with 4-carboxyphenyl film loaded with 4nitrobenzophenone and further extracted were dipped (one hour) in either in 3,4diaminobenzophenone or 4-hydroxybenzophenone. The voltammograms recorded in ACN + 0.1M NBu4BF4 with these two electrodes did not show any signal at the potential of these molecules (Ep = 0.58 V /SCE for 3,4-diaminobenzophenone and Ep = -1.3 and -1.7 V /SCE for 4-hydroxybenzophenone). This indicates a good selectivity of these grafted and loaded/extracted polycarboxyphenyl films.

Conclusion In summary, we have presented an original and simple approach for trapping functional molecules at interfaces using the diazonium salt chemistry. It relies on the one-step electrochemical functionalization of the substrates from a one-pot mixture of the functional 19 ACS Paragon Plus Environment

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molecule and the diazonium salt. This approach was demonstrated by the grafting of polycarboxyphenyl layers derived from 4-carboxybenzenediazonium tetrafluoroborate on gold and glassy carbon, in the presence of 4-nitrobenzophenone or paracetamol, as the functional molecules. The functional molecules trapped inside the film act as cross-linkers between the tethered polycarboxyphenyl chains. Their presence induces a large swelling effect of the film, which strongly collapses after extraction of the trapped molecules. Interestingly, the trapping effect is fully reversible, the functional molecules being released in acidic medium or re-trapped in their presence. Besides, the films that are prepared from a given entrapped/extracted molecule can retrap selectively this same molecule. We believe that this novel synthetic approach will not only pave a new way for the functionalization of a wide range of surfaces but also provide a simple strategy to control the trapping/release capacities of materials.

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