Anna
Barosi
a,
Avni
Berisha
b,
Claire
Mangeney
*a,
Jean
Pinson
*c,
Hamid
Dhimane
a and
Peter I.
Dalko
*a
aLaboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CNRS UMR 8601, Université de Paris, 45 rue des Saints-Pères, F-75270 Paris, France. E-mail: peter.dalko@parisdescartes.fr; claire.mangeney@parisdescartes.fr
bChemistry Department of Natural Sciences Faculty, University of Prishtina rr. “Nëna Tereze” nr. 5, 10000 Prishtina, Kosovo
cITODYS, CNRS, UMR 7086, Université de Paris, 15 rue J-A de Baïf, F-75013 Paris, France. E-mail: jean.pinson@univ-paris-diderot.fr
First published on 11th March 2021
A conceptually novel coating strategy is presented based on the selective oligomerisation of picolinium-derived end-tethered polymer chains. The remarkably rapid and nearly quantitative liberation of the covalently tethered ligand makes this system a promising candidate for the construction of densely packed “smart” release interfaces.
Scheme 1 Sequential construction of the brush-like oligomers on gold and glassy carbon surfaces by Minisci-type arylation. |
To make this system feasible, several conditions should be satisfied: (1) conditions used for the immobilization of the monomers should be compatible with the presence of the “armed” redox probes; (2) the addition of the aryl radical should be selective to the picolinium ring;21 (3) the chemical modification of the picolinium should not compromise the fragmentation ability; and (4) the electrode potential of the modified probe should be close to that of the unmodified one to avoid the sequential release of the ligand when activated.
Theoretical computations indicated that the electrochemical fragmentation of o-arylated picoliniums can be expected around E = −1.11 V vs. Ag/AgCl providing a convenient gap to find conditions for the electrochemical immobilization and activation (−0.50 V < E < −1.11 V vs. Ag/AgCl) (Scheme 2). Interestingly, according to the computation results, the o-arylation does not modify the electrode-potential of the probe (Scheme 2). Indeed, the prediction of the standard redox potential in solution (DFT) based on the use of the Born–Haber cycle of the most stable conformers22 yielded very similar values for model compound 2 and compound 1 the calculated first reduction potential of which was in good agreement with the experimental value.23
Scheme 2 DFT estimation of the first reduction potentials of model compound 2 and comparison with the calculated and experimentally observed value of 1.23 |
The retrosynthetic assembly of the redox responsive thin polymer layer-monomer is highlighted in Scheme 3.
Scheme 3 Retrosynthetic analysis of the construction of picolinium-derived monomers. P: protecting group. |
The pyrenebutyric acid ester and the azido ethyl chain were installed to picoline 3 by using a standard esterification/quaternisation sequence (Scheme 4). The protected p-ethynyl aniline, 5, was prepared in three steps starting from 4-iodoaniline. The prepared alkyne 5 was “clicked” to the azido-picolinium 4 by using Huisgen conditions affording 6 (75%), and finally the Boc group was removed by TFA. The electrochemical profile of the free aniline 7 was studied in solution by cyclic voltammetry on carbon electrodes, where the redox waves were better defined (ESI†).25 Voltammetric peaks were assigned by comparison with those of purposely-synthesized subunits of the molecule (see in ESI†).
Diazonium salt, 8, was in situ generated from 7 in an electrochemical cell by using i-pentylnitrite as the diazotization reagent and n-Bu4NBF4 (0.1 M) as the supporting electrolyte. The probe was immobilized on gold‡ and GC electrodes, by applying a potential of −0.90 V vs. Ag/AgCl to reduce the diazonium salt, while avoiding the ester cleavage (see ESI†).26 Voltammograms were recorded on GC electrodes, which give better defined voltammograms, while grafting was performed on gold, which permits the recording of IRRAS spectra). The immobilization is considered following earlier described paths: the dissociative ET results in the formation of aryl radical that first binds to the electrode surface, and then participates in chain elongation by consecutive C–H arylation, according to the Minisci path. After electrodeposition, electrodes were rinsed with ethanol under sonication and dried to give the coated materials 9@Au and 9@GC, respectively. Voltammograms before and after deposition of 7/9@GC are presented in Fig. 2.
As expected, the peak corresponding to the reduction of the aniline group, Ired, has disappeared. In contrast, peaks IIred and IIIred are detected on the coated electrode, supporting the reduction of the diazonium group of 8 (for the assignment of the fragment peaks see Table S1 in the ESI†). It is noteworthy that the intensity of peak IIIred is lower than that of IIred. This fact can be explained by the fragmentation of the pyridinium derivative during the voltammetric cycle, when the potential reaches ca. −1.2 V. Integration of the voltammogram of 9@GC provided the surface concentration of Γ = 4.0 × 10−10 mol cm−2 of the grafted molecules. This value is in agreement with the Γ = 2.5–5.7 × 10−10 mol cm−2 reported for a monolayer of nitrophenyl groups on a very flat carbon surface.16 The surface modification was characterized by IRRAS by comparing the spectra of 9@Au with that of the synthesized fragments (Fig. S5, ESI†). The most distinctive features are (i) the presence of the CO band, located at 1743 cm−1, (ii) the triazole signature that appears as two bands at 1690 and 1666 cm−1 for 7, at similar positions as that of grafted 9@Au, (iii) the aromatic ring vibrations at 1646 cm−1 of both picolinium and pyrene, and finally (iv) the C–H out-of-plane vibrations of the aromatic ring, located between 650 and 850 cm−1, particularly the strong band of pyrene at 838 cm−1. The presence of this C–H out of plane vibration band is particularly noteworthy as this band is very sensitive to substitution (this is a method to distinguish isomers); the fact that it is still present is a good indication that there is no attack on the pyrene. The IR spectra thus confirms the grafting of compound 7 on gold surface, without unwanted fragmentation/cleavage of the probe. The immobilization was also analyzed by XPS. The gold signal appeared strongly attenuated after the functionalization, while the carbon and oxygen content increased and a new peak, assigned to picolinium and triazole nitrogens appeared, indicating the coating by a polyaryl layer (see the survey spectrum in Fig. 3).
Fig. 3 XPS survey spectra of 9@Au and bare Au electrodes. The insets show the C1s and N1s high resolution spectra of 9@Au. |
The peak fitting of the C1s signal displayed in the inset of Fig. 3 reveals the presence of all the components contained in the polyaryl layer. The intense peak at 285 eV is assigned to the presence of C–C and CC bonds, the one at 286.8 eV is attributed to the C–O and C–N components, while the peak at 289.3 eV is due to the ester groups, confirming the grafting of the probe, without fragmentation. Moreover, the N1s signal is composed of two components, one at 400.4 eV corresponding to the presence of the triazole, and the one at 402.1 eV corresponding to the picolinium groups. The thickness of the grafted polyaryl layer was estimated by ellipsometry to be 8.8 ± 0.2 nm, thus indicating the formation of oligomers.
The interface between the gold electrode and the grafted probe was studied by using Surface-Enhanced Raman Spectroscopy (SERS). For this study, the probe was grafted on gold nano-island films, prepared by sputtering 5 nm of gold on indium-tin-oxide (ITO) coated-glass substrates. The SERS spectrum (Fig. 4) was recorded after thorough ultrasonic cleaning of the substrate.
Several features are noteworthy: the intense NN stretching of the diazonium group at ca. 2300 cm−1 is not observed any more indicating that the diazonium group of intermediate 8 was electrochemically removed. At the same time, one notices the appearance of a small peak at 410 cm−1, assigned to the Au–C stretching vibration,27 evidencing the covalent grafting of the aryl groups. Also, the strong band related to the stretching of aromatic CC bonds can be observed in the SERS spectra in the 1577–1630 cm−1 range. Other bands associated to the pyrene reporter28 (590 cm−1, skeletal stretch; 1060 cm−1, C–H in-plane bend; 1238 cm−1, C–C stretch/C–H in-plane bend and 1410 cm−1, C–C stretch/ring stretch) can be also recognized.
In order to simulate the SERS spectra of 9@Au, DFT calculations were performed. In this model a gold cluster with 20 atoms was used to simulate 9@Au. Fig. 4 shows the calculated structure and the simulated Raman spectrum; the Au–C bond length is estimated to be 2.317 Å with an Au–Au–C valence angle of 99.72°. A good agreement is observed between the simulated Raman and the experimental SERS spectra, with the presence of both the pyrene bands and the Au–C peak at 409 cm−1, confirming the covalent bonding of the aryl layers on the gold surface. The observed small peak frequency shifts can be attributed to the modification of the electronic structure of the grafted molecules by immobilization on the gold surface.
The modified gold plate and carbon electrodes, 9@GC and 9@Au, were subjected to reduction for 10 min, at −1.2 V/(Ag/AgCl) in ACN, in the presence of n-Bu4BF4 (0.1 M) (Fig. 5). The applied reduction potential corresponds to the reduction peak IIred of the pyridinium group that induced the irreversible fragmentation of the pyrene ester from the probe. By analyzing the electrochemical response of the electrode, one can note the absence of any signal corresponding to the pyrene group (peak IIIred), confirming the cleavage of the ester. It is worth mentioning that the electrochemical response of 7 (in solution) exhibits a reversible IIIred/IIIox peak for pyrene (Fig. 2a), indicating the absence of cleavage of this group in the time lapse of one voltammogram cycle. In contrast, this reversibility is neither observed in 9@Au (Fig. 2b) nor in 9@GC (Fig. 5a), thus indicating that the cleavage is faster than the reverse ET (oxidation). Considering, that there is no diffusion (as probes are immobilized) it is possible to estimate29 the rate of cleavage of the surface bonded pyrene group as ks ∼ 0.3 s−1 from the height of the peaks of the pyrene group in the voltammogram of 9@GC, by using a simple first order kinetic relationship (Fig. 5). Note that the degraded reversibility of the anchored pyrene signal cannot be attributed to the protonation of the radical ionic intermediate by traces of water, as the voltammogram of pyrenebutyric acid is perfectly reversible under the same conditions in solution.
The surface was also studied by IRRAS after cleavage. Fig. 5 presents the IRRAS spectra recorded before (bottom) and after (top) electrochemical reduction of 9@Au; the latter clearly shows the disappearance of the 1743 cm−1 (ester CO stretch) and 1130 cm−1 (C–O stretch) bands corresponding to the ester group, as well as the characteristic pyrene band at 847 cm−1. It is noteworthy that the 1650 cm−1 band, assigned to the picolinium group, is still present. This observation is in agreement with the cleavage between the picolinium and the pyrene (corresponding probably to the cleavage of the benzylic C–O bond, as was observed earlier).23 The presence of the free pyrene-derivative in the electrolysate was evidenced by fluorescence spectroscopy (Fig. S6, ESI†) confirming the release of pyrenebutyric acid from the covalently attached probe. The amount of the released pyrene per surface unit (Γ) was calculated by measuring the fluorescence intensity and comparing it to the calibration curve, giving Γ = 1.5 × 10−9 mol cm−2 of released pyrenebutyric acid from the gold electrode. It is noteworthy that the Γ value obtained (on gold) by the fluorescence correlation was larger than the surface concentration, estimated by electrochemistry on GC (Γ = 4 × 10−10 mole cm−2), and was assigned to the formation of oligomers on the gold surface.
Indeed, the Γ value obtained from the fluorescence correlation suggests the presence of n ∼ 4 mers. Likewise, a Γ value of n ∼ 4 mers was deduced in this experiment from ellipsometry, considering the ratio between the film thickness (8.8 nm) and the estimated monolayer thickness from molecular modeling (2.1 nm, see Fig. 4).
These results thus confirm the formation of oligomers on the electrode and also, the efficient fragmentation even at a relatively larger distance from the Au-grafting point.
Electrochemical experiments were performed using an EG&G 263A potentiostat/galvanostat and an Echem 4.30 version software. All potentials are referred to the Ag/AgCl electrode. The electrode for cyclic voltammetry was a glassy carbon (GC) rod (d = 2 mm diameter) sealed in glass. It was polished with different grades of polishing papers and finally with a 0.04 μm alumina slurry on a polishing cloth (DP-Nap, Struers, Denmark), using a Presi Mecatech 234 polishing machine. Grafting was achieved on Au coated (100 nm) Si wafers obtained from Sigma-Aldrich. Before modification, they were rinsed in concentrated sulfuric acid, ultrasonicated in Milli-Q water for 6 min, cleaned with pure ethanol, and dried under a stream of argon. For the formation of the diazonium salt 8, the ammonium salt, 7, was dissolved in ACN + 0.1 M n-Bu4BF4 (c = 2 mM). Isopentylnitrite (c = 2.4 mM) was then added and let to react for 30 min before the experiments started. All the electrochemical experiments were performed in ACN + 0.1 M n-Bu4BF4, deoxygenated with argon.
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). X-ray photoelectron spectra were recorded using a Thermo VG Scientific ESCALAB 250 system fitted with a microfocused, 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 150 and 40 eV 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. The thicknesses of the films on Au were measured using a mono wavelength ellipsometer Sentech SE400. The following values were taken for gold ns = 0.17, ks = 3.43; they were measured on the clean surfaces before grafting. The film thicknesses were determined from the same plates after modification, taking ns = 1.46, ks = 0 for the organic layer. Raman spectra were recorded using an XploRA confocal Raman instrument (HORIBA Jobin Yvon) with a 638 nm laser as the source, in backscattering mode. All spectra were taken with a 3 s integration time and recorded within the 120–1750 cm−1 spectral range. The grafted Au20 mono charged gold cluster 9@Au was modeled and used to calculate the Raman spectra. Calculations were performed with Dmol3 through generalized gradient approximations (GGE) using PBE functional30 and DNP basis set (all electron core treatment). Self-consistent iteration method (SCF)31 was used for geometry optimization (1000 iteration steps, using energy convergence of 2.0 e−5 eV per atom).
The theoretical calculation of the standard redox potential in solution is based on the use of the Born–Haber cycle. All theoretical calculations were performed using the Gaussian software.§ The geometry optimizations were performed using B3LYP functional in combination with 6-311+g(d,p) basis set. The dispersion correction was performed based on the Grimme's Dispersion DFT-D3 model. Solvent effects (acetonitrile) were included via the integral equation formalism variant (IEFPCM) approach.32
NMR 1H (CDCl3, 500 MHz): δ 8.57 (2H, dd, J = 4.5, 1.5 Hz), 8.28–8.25 (1H, m), 8.17 (2H, d, J = 8 Hz), 8.10 (2H, t, J = 8 Hz), 8.03 (2H, s), 8.00 (1H, t, J = 7.5 Hz), 7.85 (1H, m), 7.23–7.22 (2H, m), 5.86 (1H, q, J = 6.5 Hz), 3.40 (2H, t, J = 7.5 Hz), 2.54–2.50 (2H, m), 2.22 (2H, qn, J = 6.5 Hz), 1.52 (3H, d, J = 6.5 Hz). NMR 13C (CDCl3, 125 MHz): δ 172.6, 150.6, 150.3, 150.2, 135.6, 131.6, 131.0, 130.2, 129.3, 128.9, 127.6, 127.5, 127.0, 126.0, 125.3, 125.1, 125.0, 123.3, 122.0, 120.8, 70.9, 34.1, 32.8, 26.7, 22.11. MS (ESI): m/z =394.1 [M + H]+. HRMS (ESI): m/z calcd for [C27H23O2N]+ 393.1729, found 393.1735.
NMR 1H (CDCl3, 500 MHz): δ 8.69 (2H, d, J = 6.5 Hz), 8.25 (1H, d, J = 9 Hz), 8.17 (2H, d, J = 8 Hz), 8.11–8.09 (2H, m), 8.03–7.98 (3H, m), 7.84 (1H, d, J = 8 Hz), 7.64 (2H, d, J = 6.5 Hz), 5.7 (1H, q, J = 6.8 Hz), 4.69–4.66 (2H, m), 3.93 (2H, t, J = 5.5 Hz), 3.48–3.40 (2H, m), 2.55 (2H, t, J = 7.5 Hz), 2.24 (2H, qn, J = 7.5 Hz), 1.65-1.55 (2H, m), 1.46 (3H, d, J = 6.5 Hz). NMR 13C (CDCl3, 125 MHz): δ 172.2, 161.9, 145.2, 135.2, 131.5, 131.0, 130.2, 129.4, 128.9, 128.0, 127.7, 127.6, 127.0, 126.2, 125.7, 125.2, 125.1, 125.0, 124.6, 123.3, 69.9, 60.5, 50.7, 33.8, 32.7, 26.4, 21.7. MS (ESI): m/z =463.4 [M]+. HRMS (ESI): m/z calcd for [C29H27O2N4]+ 463.2129, found 463.2137.
NMR 1H (CDCl3, 500 MHz): δ 8.53 (2H, d, J = 6.8 Hz), 8.17 (1H, d, J = 9.5 Hz), 8.10 (2H, d, J = 7.5 Hz), 8.05–8.01 (3H, m), 7.95–7.92 (3H, m), 7.75 (1H, d, J = 8 Hz), 7.57 (2H, d, J = 8.5 Hz), 7.51 (2H, d, J = 6.5 Hz), 7.30 (2H, d, J = 8.5 Hz), 6.73 (1H, s), 5.60 (1H, q, J = 6.5 Hz), 5.15–5.12 (2H, m), 5.00–4.98 (2H, m), 3.37–3.24 (2H, m), 2.44 (2H, t, J = 7 Hz), 2.12 (2H, qn, J = 7 Hz), 1.48 (9H, s), 1.32 (3H, d, J = 6.5 Hz). NMR 13C (CDCl3, 125 MHz): δ 172.1, 161.9, 152.9, 148.0, 146.9, 145.1, 138.8, 135.3, 131.4, 130.9, 130.1, 128.8, 127.6, 127.5, 126.9, 126.4, 126.1, 125.1–124.7 (7C), 123.3, 122.0, 119.4, 69.8, 60.3, 36.4, 33.7, 32.6, 28.5, 26.3, 21.5, 14.9. MS (ESI): m/z =680.1 [M]+. HRMS (ESI): m/z calcd for [C42H42O4N5]+ 680.3231, found 680.3224.
NMR 1H (CDCl3, 250 MHz): δ 8.55 (2H, d, J = 6.8 Hz), 8.32 (1H, s), 8.13 (1H, d, J = 6.8 Hz), 8.05 (2H, d, J = 8.3 Hz), 8.00–7.85 (7H, m), 7.71 (3H, m), 7.41 (2H, d, J = 8.5 Hz), 5.65 (1H, q, J = 6.8 Hz), 5.01 (4H, m), 3.26–3.17 (2H, m), 2.45 (2H, t, J = 7 Hz), 2.04 (2H, qn, J = 7 Hz), 1.35 (3H, d, J = 6.8 Hz). NMR 13C (CDCl3, 125 MHz): δ 173.7, 164.0, 149.4, 146.2, 136.9, 132.8, 132.2, 131.4, 129.9, 128.7, 128.6, 128.4, 127.9, 127.7, 127.3, 127.1, 126.1–125.9 (5C), 124.4, 124.2, 123.1, 122.4, 119.0, 71.4, 61.3, 50.9, 34.5, 33.5, 27.6, 21.7. MS (ESI): m/z =581.1 [M]+. HRMS (ESI): m/z calcd for [C37H35O2N5]+ 581.2780, found 581.2771.
Footnotes |
† Electronic supplementary information (ESI) available. See DOI: 10.1039/d1ma00022e |
‡ Gold plated silicon wafers were selected as support due to their reflective properties, facilitating the characterization by infra-red reflection–absorption spectroscopy (IRRAS) and ellipsometry.)24 |
§ All theoretical calculations were performed using the Gaussian software.22 The geometry optimizations were performed using B3LYP functional in combination with the 6-311+g(d,p) basis set. The dispersion correction was performed based on Grimme's Dispersion DFT-D3 model. Solvent effects (acetonitrile) were included via the integral equation formalism variant (IEFPCM) approach. |
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