Electrochemical "switching" of Si(100) modular assemblies

Article abstract of DOI:10.1021/ja210048x

We report on a modular approach for producing well-defined and electrochemically switchable surfaces on Si(100). The switching of these surfaces is shown to change a Si(100) surface from resistant to cell adsorption to promoting cell adhesion. The electrochemical conversion of the modified electrode surface is demonstrated by X-ray photoelectron spectroscopy, X-ray reflectometry, contact angle and cell adhesion studies.

Full text of DOI:10.1021/ja210048x

Supporting Information for
Electrochemical ‘Switching’ of Silicon(100) Modular Assemblies
Simone Ciampi, Michael James, Guillaume Le Saux, Katharina Gaus, and J. Justin Gooding*
Scheme S1. ‘Trimethyl-lock’. Structural requirement for a facile lactonization reaction in hydroquinone derivatives.
Methyl groups involved in the ‘trimethyl lock’ scheme are highlighted in bold.1-3
Figure S1. High resolution XPS data for the Si 2p region. When present, the fractional monolayer coverage of
oxidized silicon was calculated directly from the oxidized/bulk Si 2p peak area ratio to the method described by
Lewis and co-workers for very thin oxide overlayers (ref. 21 and ref. 22 in the SI). According to the method, the
spectrometer detection limit can be approximated to ca. 0.06 SiOx ML equivalents.
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Table S1. Refined Thickness (d), Interfacial roughness () and Scattering Length Density (SLD) from
XRR Data
‘switched’ surfacea
SAM-1
9.6 (0.5)c
1.7
SAM-2
22.2 (0.5)
3.4
SAM-3
18.2(0.8)
2.2
d (Å)
19.5 (0.8)
3.0
Si (Å)
5.1
10.2
6.2
3.2

film (Å)
SLD (× 10‒ 6Å–2)b
10.4
10.5
14.8
10.5
a SAM-2, putative product for the ‘switch’ of SAM-3
b for X-rays, electron density [e‒ Å‒ 3] of the material are obtained by dividing SLD values by a factor 2.82 × 10–
5 Å
c Esd`s from the fits are in parenthesis
Figure S2. X-ray reflectometry spectra acquired on ‘click’ functionalized SAM-2 samples.
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S1. Experimental Section
S1.1 Materials
S1.1.1 Chemicals. All chemicals, unless noted otherwise, were of analytical grade and used as
received. Chemicals used in surface modification procedures and electrochemical experiments
were of high purity (≥ 99%). Hydrogen peroxide (30 wt.% sol. in water, Sigma-Aldrich),
hydrofluoric acid (Riedel-de Haën, 48 wt.% sol. in water), and sulfuric acid (J. T. Baker) used in
wafers cleaning and etching procedures were of semiconductor grade. 1,8-Nonadiyne (Alfa
Aesar, 97%) was redistilled from sodium borohydride (Sigma-Aldrich, 99+%) under reduced
pressure (80 ºC, 8−9 Torr) and stored under a high purity argon atmosphere (H2O < 10 ppb, O2 <
5 ppb) prior to use. Milli-Q™ water (> 18 MΩ cm) was used to prepare solutions and for
chemical reactions. Dichloromethane, chloroform, hexane, light petroleum (b.p. 60−80 ºC),
acetone, 2-propanol, ethanol, methanol and ethyl acetate for surface cleaning, chemical reactions
and purification procedures were redistilled prior to use. Anhydrous solvents used in chemical
reactions were purified as follows: (a) dichloromethane was distilled from calcium hydride; (b)
pyridine was distilled under reduced pressure from potassium hydroxide; (c) N,N-
dimethylformamide was distilled under reduced pressure from calcium hydride; (d)
tetrahydrofuran was distilled from sodium using a benzophenone indicator; (e) 2-propanol was
distilled from sodium; (f) 1,4-dioxane was distilled from sodium; (g) carbon tetrachloride was
distilled from phosphorus pentoxide; (h) diethyl ether was distilled from sodium using a
benzophenone indicator; (i) ethanol was distilled from sodium; (l) toluene was distilled under
reduced pressure from calcium hydride. p-Toluensulfonyl chloride (Sigma-Aldrich, 98%) was
recrystallized from chloroform/hexane. Sodium azide (Sigma-Aldrich, 98%) was crystallized
from water by the addition of ethanol. ,-Dimethylacrylic acid (Sigma-Aldrich, 97%) was
recrystallized from light petroleum. Chloromethyl methyl ether was of technical grade (Sigma).
Dulbecco’s Phosphate Buffered Saline (DPBS, pH 7.4) was prepared from potassium chloride
(2.7 mM), sodium chloride (117 mM), potassium dihydrogenphosphate (1.5 mM) and sodium
monohydrogenphosphate (8 mM).
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S1.1.2 Silicon Wafers. Prime grade double-side polished silicon wafers, 100-oriented (<100>
± 0.9°), p-type (boron-doped), 500 ± 25 μm thick, <0.007–0.009 Ω cm resistivity, were obtained
from Virginia Semiconductors, Inc. (VA, USA).
S1.2 Purification and Analysis of Synthesized Compounds. Thin-layer chromatography
(TLC) was performed on Merck silica gel aluminum sheets (60 F254). Davisil®LC 60 Å silica
gel (40−60m) was used for column chromatography. Unless otherwise specified NMR spectra
were recorded on a Bruker Avance 300 spectrometer in deuteriochloroform (CDCl3 from
Aldrich, passed through basic alumina) using the solvent signal as an internal reference. FTIR
spectra were recorded on a Thermo Nicolet Avatar 370 FTIR spectrometer by accumulating a
minimum of 32 scans and selecting a resolution of 2 cm−1. Scheme S2 describes the synthetic
procedure for the preparation of the redox-sensitive lactone linker 2 in ten steps (i–x) from
commercially available 2,5-dimethylphenol a, following in part literature procedures4-6 with
major modifications for some of the synthetic steps. 2-(2-(2-Methoxyethoxy)ethoxy)ethanamine
3 was obtained from the hydroxyl precursor, triethylene oxide monomethyl ether m, in a three-
step (i–iii) synthetic sequence (Scheme S3) via triphenylphosphine-mediated reduction of the
azide intermediate.7
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Scheme S2. Synthesis of the redox-sensitive lactone linker 2
i. Na2CrO4, H2SO4/Et2O, 49%; ii. Na2S2O4, 93%; iii. ,-dimethylacrylic acid, CH3SO3H, 86%; iv. allyl bromide,
K2CO3, NaI, 69%; v. BCl3-heptane, 72%; vi. MOMCl, DIPEA, 63%; vii. BH3-hexane, NaOH/H2O2, 45%; viii. TsCl,
Py, 62%; ix. NaN3, 73%; x. CBr4, 84%.
7-(3-Azidopropyl)-6-hydroxy-4,4,5,8-tetramethylhydrocoumarin (2)
(i) 2,5-Dimethylbenzoquinone (b). The alkylquinone b was prepared from 2,5-dimethylphenol
a in a one-pot procedure via a two-phase Jones oxidation reaction according to literature
procedures6 with minor modifications. 2,5-Dimethylphenol a (30.0 g, 246 mmol) was dissolved
in diethyl ether (ca. 400 mL) and the solution cooled to 0° C in an ice/water bath. The reaction
flask was equipped with a mechanical stirrer and a dropping funnel. The Jones reagent was
prepared in the dropping funnel from sodium dichromate dihydrate (150.0 g, 503 mmol) by
adding to it ice-cold water (155 mL) and 96% sulphuric acid (68 mL) with vigorous shaking.
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Addition of the Jones reagent to the solution of the phenol a was done dropwise over a 2 h period
while stirring. After the addition the ice bath was removed and stirring was continued at room
temperature for a 36 h period. The reaction mixture was transferred to a separation funnel and
extracted with diethyl ether (4 × 100 mL). The combined organic extracts were washed with
saturated sodium bicarbonate solution (2 × 100 mL), water (200 mL) and dried over MgSO4.
Filtration through celite and evaporation of the solvent in vacuo afforded crude quinone b as a
dark orange oil. Precipitation from ice cold light petroleum followed by column chromatography
1
(ethyl acetate/light petroleum, 1:4) gave the quinone b as a yellow powder (16.4 g, 49%). H
NMR (300 MHz, CDCl3) : 6.59 (bs, 2H), 2.02 (s, 6H); 13C NMR (75.5 MHz, CDCl3) : 188.16,
145.92, 133.49, 15.61; IR (KBr, cm−1): 1665, 1643, 1611, 1438, 1380, 1349, 1254, 1154, 1005,
927, 796.
(ii) 2,5-Dimethylhydroquinone (c). Reduction of the alkylquinone b to the corresponding
hydroquinone
was
done
according
to
literature
procedure.4
2,5-Dimethylbenzoquinone b (16.0 g, 118 mmol) was dissolved in diethyl ether (ca. 200 mL)
and the solution obtained transferred to a separation funnel previously loaded with sodium
hydrosulfite (150 g, 0.86 mol) and water (150 mL). The mixture was shaken until the organic
layer had turned nearly colourless. The ether layer was then collected and the aqueous phase
extracted with ether (3 × 50 mL). The pooled organic phase was washed with brine (2 × 50 mL),
dried over MgSO4, filtered and dried in vacuo to give the quinone c (15.2 g, 93%) as a white
1
residue used in the successive step without further purification. H NMR (300 MHz, DMSO-d6)
13
: 8.31 (bs, 2H), 6.45 (s, 2H), 1.99 (s, 6H); C NMR (75.5 MHz, DMSO-d6) : 147.46, 121.17,
116.87, 15.77; IR (KBr, cm−1): 3246, 1427, 1189, 1186, 868, 827, 688.
(iii) 6-Hydroxy-4,4,5,8-tetramethylhydrocoumarin (d). Alkylhydroquinone c was converted to
lactone d by reaction with dimethylacrylic acid in a Friedel-Craft type addition reaction.4-5 ,-
Dimethylacrylic acid (12 g, 120 mmol) was added to a solution of 2,5-dimethylhydroquinone c
(15 g, 110 mmol) in methanesulfonic acid (ca. 170 mL) and the obtained solution stirred for 3 h
at 70−80 C under an argon atmosphere. The crude reaction mixture was allowed to cool to room
temperature and subsequently ice (ca. 200 g) was slowly added into the reaction flask to give a
gray suspension which was allowed to warm to room temperature before being extracted with
ethyl acetate (3 × 50 mL). The pooled organic layers were washed with saturated sodium
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bicarbonate solution (2 × 50 mL), water (2 × 50 mL) and then dried over MgSO4. Upon filtration
and evaporation in vacuo a white residue was obtained. The crude title compound was dissolved
in a minimum amount of warm ethyl acetate and crystallization upon the addition of ice-cold
1
hexane yielded the coumarin d as a off-white powder (20.9 g, 86%). H NMR (300 MHz,
13
CDCl3) : 6.56 (s, 1H), 4.84 (s, 1H), 2.56 (s, 2H), 2.33 (s, 3H), 2.22 (s, 3H), 1.46 (s, 6H); C
NMR (75.5 MHz, CDCl3) : 168.63, 150.17, 143.66, 131.08, 124.68, 119.60, 115.79, 45.82,
35.57, 27.51, 16.03, 13.93.; IR (KBr, cm−1): 3378, 2977, 2948, 1734, 1615, 1466, 1318, 1245,
1159, 1120, 1022.
(iv)
6-(Allyloxy)-4,4,5,8-tetramethylhydocoumarin
(e).
6-Hydroxy-4,4,5,8-
tetramethylhydrocoumarin d (20.0 g, 90.8 mmol), potassium carbonate (26.3 g, 190 mmol) and
sodium iodide (0.3 g, 2.0 mmol) were suspended in acetone (ca. 100 mL). Allyl bromide (23 g,
190 mmol) was added to the reaction mixture in one portion while stirring at room temperature.
The suspension was then heated at 60 °C while stirring for 5.5 days under argon. Additional allyl
bromide (3 × 2.4 g) was added after 1, 2 and 3 days. After cooling of the reaction mixture to
room temperature and evaporation of the solvent in vacuo, the crude title compound e was
recovered as dark yellow oil. The obtained residue was then dissolved in dichloromethane and
washed with water (100 mL). The aqueous phase was further extracted with dichloromethane (2
× 50 mL) and the pooled organic layers washed with water (2 × 50 mL) before drying over
MgSO4. Filtration through celite and evaporation of the solvent in vacuo afforded the crude
coumarin e as a orange/brown residue. Column chromatography (dichloromethane) gave the pure
1
product e (16.3 g, 69%) as a pale yellow solid. H NMR (300 MHz, CDCl3) : 6.62 (s, 1H),
6.13−6.00 (m, 1H), 5.42 (dd, 1H, J = 1.5 Hz, J = 17.3 Hz ), 5.28 (dd, 1H, J = 1.5 Hz, J = 10.6 Hz
), 4.49 (d, 2H, J = 5.3 Hz ), 2.56 (s, 2H), 2.35 (s, 3H), 2.26 (s, 3H), 1.46 (s, 6H); 13C NMR (75.5
MHz, CDCl3) : 168.93, 153.58, 144.16, 133.88, 131.47, 124.54, 123.11, 117.44, 113.73, 70.15,
46.35, 36.07, 27.96, 16.88, 14.46; IR (KBr, cm−1): 2956, 1760, 1607, 1467, 1323, 1276, 1246,
1192, 1163, 1124, 1029, 916.
(v)
7-Allyl-6-hydroxy-4,4,5,8-tetramethylhydrocoumarin
(f).8
6-(Allyloxy)-4,4,5,8-
tetramethylhydocoumarin e (15.5 g, 59.6 mmol) was dissolved in dichloromethane and the
solution stirred at 0 °C under argon. An ice cold 1.0 M solution of boron trichloride in heptane
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(100 ml, 100 mmol) was added dropwise via a dropping funnel to the reaction mixture over a 10
min period. Stirring was continued at 0 °C for an additional 4 h and then at room temperature for
12 h. Ice cold saturated sodium bicarbonate solution (ca. 100 mL) was then added to the reaction
mixture with vigorous stirring over an ice-water bath. The organic phase was separated and
washed with water (2 × 50 mL), dried over MgSO4, filtered and evaporated in vacuo to afford
the crude f as yellow oil. Column chromatography (dichloromethane) gave the pure product f
1
(11.2 g, 72%) as a yellow solid. H NMR (300MHz, CDCl3) : 6.00−5.88 (m, 1H), 5.16−5.05
(m, 2H), 4.79 (s, 1H), 3.43 (d, 2H, J = 5.7 Hz), 2.55 (s, 2H), 2.35 (s, 3H), 2.22 (s, 3H), 1.45 (s,
13
6H); C NMR (75.5 MHz, CDCl3) : 168.84, 149.41, 143.85, 135.05, 129.32, 123.43, 123.38,
120.11, 116.51, 46.14, 35.69, 31.43, 27.79, 14.48, 12.36; IR (KBr, cm−1): 3405, 3010, 2958,
1743, 1636, 1444, 1287, 1261, 1214, 1190, 1127, 1038, 902.
(vi) 7-Allyl-6-(methoxymethoxy)-4,4,5,8-tetramethylhydrocoumarin (g). 7-Allyl-6-hydroxy-
4,4,5,8-tetramethylhydrocoumarin f (10.5 g, 40.3 mmol) was added to solution of
diisopropylethylamine (44 mL, 252 mmol) in dry dichloromethane (ca. 150 mL) while stirring
under an argon. The reaction flask was then cooled in an ice/water bath before adding dropwise
ice cold chloromethyl methyl ether (15.3 mL, 177 mmol) over a 30 min period. One hour after
the addition was complete the reaction mixture was allowed to warm up to room temperature and
stirring was continued for an additional 5 h. The crude mixture was then diluted with
dichloromethane (100 mL), washed with ice cold 3 M hydrochloric acid (2 × 20 mL), ice cold
water (2 × 50 mL), dried over MgSO4 and filtered. The solvent was removed in vacuo and the
residue purified by column chromatography (ethyl acetate/light petroleum, 1:2) to give the
methoxymethyl protected product g as a white solid (7.73 g, 63%). 1H NMR (300 MHz, CDCl3)
: 5.97−5.88 (m, 1H), 5.04 (dd, 1H, J = 1.9 Hz, J = 10.2 Hz), 4.92 (dd, 1H, J = 1.9 Hz, J = 18.5
Hz), 4.89 (s, 2H), 3.60 (s, 3H), 3.48 (d, 2H, J = 5.6 Hz), 2.56 (s, 2H), 2.40 (s, 3H), 2.21 (s, 3H),
13
1.45 (s, 6H); C NMR (75.5 MHz, CDCl3) : 173.07, 168.53, 151.54, 146.44, 136.06, 131.41,
129.32, 126.93, 124.61, 115.59, 100.17, 57.71, 46.04, 35.82, 31.72, 27.66, 15.89, 12.47; IR
(KBr, cm−1): 3013, 2971, 1764, 1636, 1435, 1388, 1248, 1154, 1168, 1154, 1041, 982.
(vii)
7-(3-Hydroxypropyl)-6-(methoxymethoxy)-4,4,5,8-tetramethylcoumarin
(h).4
7-Allyl-6-(methoxymethoxy)-4,4,5,8-tetramethylhydrocoumarin g (7.50 g, 24.6 mmol) was
dissolved in anhydrous tetrahydrofuran (ca. 200 mL) and the solution stirred vigorously for 20
S - 8 -

min while bubbling argon through it. The reaction mixture was then cooled in an ice/water bath
before adding dropwise a large excess of 1.0 M borane hydride–tetrahydrofuran solution (40 mL,
40 mmol) over a 30 min period under argon. After the addition was complete, the mixture was
stirred at 0 °C for 20 min under inert atmosphere. The reaction mixture was then allowed to
warm to room temperature and stirring was continued for an additional 12 h under argon. Upon
cooling of the reaction mixture to 0 °C in an ice bath 3 M sodium hydroxide solution (7 mL, 21
mmol) and 30% hydrogen peroxide solution (7 mL, 62 mmol) were simultaneously added
dropwise to the reaction mixture from separate dropping funnels while stirring was continued.
The reaction was continued for 5 min before removing the ice bath. Stirring was continued under
ambient atmosphere at room temperature for an additional 1 h. The crude mixture was diluted
with ethyl acetate (100 mL) and then transferred into a separation funnel where water (ca. 20
mL) was added. Hydrochloric acid (3 M) was added to reduce the solution ca. pH 5. When
bubbling was significantly reduced, but still present, the water layer was removed and the
organic layer further washed with water (ca. 50 mL). The aqueous layer was then extracted with
ethyl acetate (2 × 25 mL) and the pooled organic phase washed with water (2 × 25 mL), brine
(25 mL), dried over MgSO4 and filtered. The solvent was then evaporated in vacuo and the
residue purified by column chromatography (ethyl acetate/light petroleum, 2:1) to give the
coumarin h as a white solid (3.58 g, 45%). 1H NMR (300 MHz, CDCl3) : 4.90 (s, 2H), 3.63 (s,
3H), 3.57 (t, 2H, J = 6.0 Hz ), 2.81 (t, 2H, J = 7.1 Hz), 2.55 (s, 2H), 2.38 (s, 3H), 2.24 (s, 3H),
1.76 (m, 2H), 1.44 (s, 6H); 13C NMR (75.5 MHz, CDCl3) : 168.41, 151.45, 146.68, 133.37,
129.02, 126.54, 123.93, 100.19, 61.85, 57.91, 45.95, 35.74, 32.22, 27.61, 23.42, 15.85, 12.39; IR
(KBr, cm−1): 3417, 2952, 1766, 1666, 1600, 1470, 1417, 1318, 1246, 1159, 1040, 980.
(viii)
3-(6-(methoxymethoxy)-4,4,5,8-tetramethylcoumarin-7-yl)
propyl
4-
methylbenzenesulfonate
(i). 7-(3-Hydroxypropyl)-6-(methoxymethoxy)-4,4,5,8-
tetramethylcoumarin h (3.20 g, 9.93 mmol) was dissolved in dry pyridine (6 mL) and dry
dichloromethane (20 mL) and the stirred solution cooled in an ice/water bath under an argon
atmosphere. p-Toluensulfonyl chloride (2.08 g, 10.9 mmol) was added in one portion and the
reaction continued under inert gas for 3 h at 0 °C and for an additional 12 h at room temperature.
The crude mixture was transferred to a separation funnel and diluted with ice (ca. 50 g) before
adding dichloromethane (100 mL) and ice cold 3 M hydrochloric acid (50 mL). The organic
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layer was separated and then further washed with ice-cold 3 M hydrochloric acid (3 × 50 mL),
water (50 mL), dried over MgSO4 and filtered. Drying in vacuo left a pale yellow oil who was
purified by column chromatography (ethyl acetate/light petroleum, 1:2) to give the title
1
compound i as a off-white solid (2.93 g, 62%). H NMR (300 MHz, CDCl3) : 7.80 (d, 2H, J =
8.1 Hz), 7.35 (d, 2H, J = 8.1 Hz), 4.85 (s, 2H), 4.10 (t, 2H, J = 6.0 Hz), 3.57 (s, 3H), 2.71 (t, 2H,
13
J = 7.9 Hz), 2.54 (s, 2H), 2.45 (s, 3H), 2.34 (s, 3H), 1.84 (m, 2H), 1.43 (s, 6H); C NMR (75.5
MHz, CDCl3) : 172.52, 168.01, 151.45, 144.48, 132.87, 132.28, 129.54, 128.89, 127.61,
126.29, 123.23, 99.75, 70.10, 57.29, 45.49, 35.32, 28.55, 27.14, 27.61, 23.43, 21.36, 15.48,
11.97.
(ix) 7-(3-Azidopropyl)-6-(methoxymethoxy)-4,4,5,8-tetramethylcoumarin (l). To a solution of
3-(6-(methoxymethoxy)-4,4,5,8-tetramethylcoumarin-7-yl) propyl 4-methylbenzenesulfonate i
(2.50 g, 5.25 mmol) in N,N-dimethylformamide (21 mL) and water (14 mL), sodium azide (2.94
g, 45 mmol) was added in one portion with stirring at room temperature. The obtained
suspension was warmed to 60 C in an oil bath and stirred under an argon atmosphere for 16 h.
The mixture was concentrated in vacuo (bath temperature not exceeding 60 C) to leave a off-
white slurry which was then suspended in ca. 80 mL of ethyl acetate. Excess sodium azide was
removed by filtration. The filtrate was evaporated in vacuo and the crude product was purified by
column chromatography (ethyl acetate/light petroleum, 2:1) to give the substituted azide l as a
white solid (1.33 g, 73%). 1H NMR (300 MHz, CDCl3) : 4.89 (s, 2H), 3.63 (s, 3H), 3.36 (t, 2H,
J = 6.4 Hz), 2.76 (t, 2H, J = 7.9 Hz), 2.55 (s, 2H), 2.36 (s, 3H), 2.23 (s, 3H), 1.78 (m, 2H), 1.44
(s, 6H); 13C NMR (75.5 MHz, CDCl3) : 168.52, 151.82, 146.47, 133.10, 129.21, 126.71,
123.68, 100.17, 57.72, 51.55, 45.93, 35.75, 28.98, 27.58, 24.87, 15.95, 12.46.
(x) 7-(3-Azidopropyl)-6-hydroxy-4,4,5,8-tetramethylhydrocoumarin (2). To a stirred solution
of 7-(3-azidopropyl)-6-(methoxymethoxy)-4,4,5,8-tetramethylhydrocoumarin l (1.01 g, 2.91
mmol) in anhydrous 2-propanol (250 mL) carbon tetrabromide (200 mg, 0.603 mmol) was added
in one portion while stirring under argon. The reaction mixture was heated to ca. 80 °C and
stirring was continued for 12 h. The reaction mixture was evaporated in vacuo and the crude
yellow oil was purified via column chromatography (ethyl acetate/light petroleum, 2:1) to afford
the title compound 2 as white solid (741 mg, 84%). 1H NMR (300 MHz, CDCl3) : 5.16 (s, 1H),
3.36 (t, 2H, J = 6.4 Hz), 2.75 (t, 2H, J = 7.1 Hz), 2.55 (s, 2H), 2.35 (s, 3H), 2.23 (s, 3H), 1.83 (m,
S - 10 -

2H), 1.45 (s, 6H); 13C NMR (75.5 MHz, CDCl3) : 168.72, 149.15, 143.87, 129.05, 125.15,
123.34, 119.62, 50.97, 46.17, 35.68, 28.08, 27.84, 23.55, 14.69, 12.29; IR (KBr, cm−1): 3437,
2924, 2111, 1732, 1634, 1455, 1412, 1303, 1259, 1189, 1127, 1032.
Scheme S3. Synthesis of the oligoether 3
i. TsCl, 34%; ii. NaN3, 63%; iii. PPh3, 56%.
2-(2-(2-Methoxyethoxy)ethoxy)ethanamine (3)
(i)
2-(2-(2-Methoxyethoxy)ethoxy)ethyl
4-methylbenzenesulfonate
(n).
2-(2-(2-
Methoxyethoxy)ethoxy)ethanol m (2.01 g, 12.2 mmol) was added to a solution of anhydrous
pyridine (5 mL) and anhydrous dichloromethane (15 mL). The solution was cooled on an ice-
water bath, under an argon atmosphere, and p-toluensulfonyl chloride (2.85 g, 15 mmol) was
added in one portion with stirring. Stirring was continued under argon at room temperature for
24 h. The reaction mixture was evaporated in vacuo and the crude material purified using column
chromatography (ethyl acetate/methanol, 10:1) to afford sulfonate n as a colourless oil (1.3 g,
34%). 1H NMR (300 MHz, CDCl3) δ: 7.78 (d, 2H, J = 8.5 Hz), 7.33 (d, 2H, J = 8.5 Hz), 4.14 (t,
2H, J = 4.6 Hz), 3.65 (m, 10H), 3.34 (s, 3H), 2.43 (s, 3H).
(ii) 1-Azido-2-(2-(2-methoxyethoxy)ethoxy)ethane (o). To a solution of the tosylated glycol n
(1.2 g, 3.8 mmol) in N,N-dimethylformamide (10 mL) and water (5 mL), sodium azide (1.3 g, 20
mmol) was added in one portion while stirring. The suspension was heated to ca. 60C and
stirring was continued for 16 h. The mixture was evaporated in vacuo and the resulting residue
was suspended in ethyl acetate (ca. 50 mL), filtered and the filtrate concentrated. The crude
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product was purified using column chromatography (ethyl acetate/light petroleum, 5:1) to give
the title compound o as a colourless oil (450 mg, 63%). 1H NMR (300 MHz, CDCl3) δ: 3.65 (m,
10H), 3.55 (t, 2H, J = 2.6 Hz), 3.36 (s, 3H); 13C NMR (75.5 MHz, CDCl3) : 72.06, 70.85, 70.78,
70.74, 70.16, 59.17, 50.81; IR (NaCl, cm−1): 2874, 2104, 1678, 1452, 1347, 1286, 1248, 1199,
1109, 1029.
(iii) 2-(2-(2-methoxyethoxy)ethoxy)ethanamine (3). A stirred solution of 1-azido-2-(2-(2-
methoxyethoxy)ethoxy)ethane o (380 mg, 2.01 mmol) in anhydrous tetrahydrofuran (ca. 20 mL)
was cooled on an ice-water bath under argon atmosphere. Triphenylphosphine (580 mg, 2.21
mmol) was added in one portion and stirring was continued at room temperature for 3 days.
Water (ca. 5 mL) was added to the solution to hydrolyze the putative phosphorous intermediate9
and stirring was continued at room temperature for an additional 24 h. Water was added (ca. 10
mL) and the crude reaction mixture concentrated to remove most of the organic solvent. The
solution pH was adjusted with 3 M hydrochloric acid to ca. 3 and toluene (5 mL) was added. The
solution was transferred to a separatory funnel, the organic phase separated and the aqueous
layer further washed with toluene (2 × 5 mL). The pooled water phase was evaporated in vacuo
to give a pale yellow oil which was purified using column chromatography (ethyl
1
acetate/methanol, 9:1) to give the title compound 3 as a colourless oil (182 mg, 56%). H NMR
(300 MHz, CDCl3) δ: 3.60 (m, 10H), 3.17 (t, 2H, J = 2.8 Hz), 3.34 (s, 3H); 13C NMR (75.5 MHz,
CDCl3) : 73.36, 70.75, 70.69, 70.44, 70.14, 59.20, 41.85.
S1.3 Surface Modification. Assembly of the redox-sensitive surfaces SAM-2 and anti-fouling
surface SAM-3 followed synthetic procedures depicted in Figure 1. The dormant10 lactone linker
molecule 2 was attached to the acetylenyl Si(100) surface through a Cu(I)-catalyzed alkyne-azide
cycloaddition reaction.11-13 Chemical oxidation of the confined lactone moiety to the
corresponding benzoquinone acid was followed by its activation with carbodiimides and N-
hydroxysuccinimide to promote reactions of the exposed acid function toward nucleophiles. 2-
(2-(2-Methoxyethoxy)ethoxy)ethanamine 3 was attached to the activated construct via
conventional amide coupling procedures.14
S1.3.1 Acetylene-functionalized Silicon(100) Surface (SAM-
1). Assembly of the acetylenylated Si(100) surface by covalent
S - 12 -

attachment of the diyne 1 followed a previously reported procedure.12, 15-16 In brief, Silicon
wafers were cut into pieces (approximately 10 × 20 mm), cleaned for 30−40 min in hot Piranha
solution (100 °C, 1 vol 30% by mass aqueous hydrogen peroxide/3 vol sulfuric acid), before
being transferred first to an aqueous fluoride solution (2.5% hydrofluoric acid, 1.5 min).
Subsequently, the samples were transferred, taking extra care to exclude air completely from the
reaction vessel (a custom-made Schlenk flask), to a degassed (through a minimum of 4 freeze–
pump–thaw cycles) sample of diyne 1. The samples were kept under a stream of argon (H2O <
10 ppb, O2 < 5 ppb) while the reaction vessel was immersed in an oil bath set to 165 °C for 3 h.
The flask was then opened to the atmosphere, and the functionalized surface samples (SAM-1)
were rinsed several times with dichloromethane and rested for a 12-h period in a sealed vial at +4
°C under dichloromethane, before being either analyzed or further reacted with the redox linker
molecule 2.
S1.3.2 Attachment of the Redox-Sensitive
Linker 2 to the Acetylenyl Surface (SAM-2).
In a typical ‘click’ procedure, to a reaction vial
containing the alkyne-functionalized silicon
surface (SAM-1) were added (i) the azide 2 (10
mM, 2-propanol/water, 2:1), (ii) copper(II) sulfate pentahydrate (1 mol% relative to the azide 2)
and (iii) sodium ascorbate (10 mol% relative to the azide 2). Reactions were carried out at 35 °C,
in the dark without excluding air from the reaction environment and stopped after 12 h by
removal of the modified sample from the reaction vessel.17 The prepared surface-bound [1,2,3]-
triazoles samples (SAM-2) were rinsed consecutively with copious amounts of water and
ethanol, and then rested at room temperature for a 1-min period in a 0.5 M hydrochloric acid
solution. Samples were then rinsed with copious amounts water before being either analyzed or
further reacted. Rinsing of the samples with 0.05% (w/v) ethylenediaminetetraacetic acid
solution EDTA was inefficient in removing traces of residual copper catalyst. A significant Cu
2p3/2 emission at ca. 933 eV (e.g. 0.2 to 0.5% of the total carbon for SAM-2) was evident in
survey scans (Figure S3a) after the EDTA wash. Complete removal of adventitious copper
required a brief exposure (1-min) of the triazole-functionalized samples to a 0.5 M hydrochloric
acid solution (Figure S3b-c). The hydrolytic stability of the triazole moiety is well-
documented,12, 18 and no evidences were found of an ipso (“at the same”) substitution reaction at
S - 13 -

the surfacial sylilated olefin (Si–C=C), event eventually leading to a complete removal of the
film. The relative abundance of Cu(I) and Cu(II) species was assessed on the basis of the
decomposition procedure of the Cu 2p3/2 photoelectron emission (to which both species
contribute) as proposed by Cerofolini and co-workers.19-20 As shown in Figure S3c, a high-
quality fit (reduced χ2) to the experimental high-resolution XPS curve required a two-function
model (100% Gaussian lines). The integrated area under the relatively narrow (1.6 eV fwhm)
signal centered at 933.4 eV, ascribed to Cu(I) species, was compared to the integrated area under
the broader Cu(II) contribution (2.0 eV fwhm) at 935.0 eV to give an 20:1 ratio for the
Cu(I)/Cu(II) couple. The Auger copper parameter derived from the relative spectral positions of
the Cu LMM Auger line (572.9 eV) and the Cu 2p3/2 photoelectron signal (ca. 933 eV) was
consistent with a predominant Cu(I) population. The calculated Auger parameter, close to
1847.5, was plotted in a Wagner diagram to compare our experimental data with those reported
for various Cu(I) salts. The obtained XPS data strongly suggested the ability of the organic
modified surface (SAM-2) to chelate Cu(I) ions.
Figure S3. (a-b) Traces of residual copper catalyst (a) were effectively removed through exposure of the modified
surface to a 0.5 M hydrochloric acid solution (b).Deconvolution of the experimental curve for the Cu 2p3/2 emission
supports the presence of a predominant Cu(I) population (c).
S1.3.3 Oxidation of Confined Lactone
Moieties to Benzoquinone Acids and
their Activation with NHS. Lactone-
functionalized surface samples (SAM-2)
were rinsed with tetrahydrofuran (ca. 50
S - 14 -

mL) and then transferred to a mixture of tetrahydrofuran (6 mL) and water (3 mL). N-
Bromosuccinimide (160 mg, 90 mmol) was added to the reaction vial and the solution agitated
for 3 h in the dark at room temperature. The putative ring-opened,4 benzoquinone acid
intermediate was then copiously rinsed with water, tetrahydrofuran and ethanol before being
transferred to a reaction flask charged with N-(3-dimethylpropyl)-N'-ethylcarbodiimide
hydrochloride (200 mg, 1.04 mmol) and N-hydroxysuccinimide (240 mg, 2.09 mmol ). Water
(10 mL) was added to the flask and the uncapped vessel shaken in the dark for 3 h at room
temperature. The activated21 silicon samples were removed from the reaction mixture and
washed with copious amounts of water and ethanol before being further reacted.
S1.3.4 General Procedure for
the Reactions of Activated
Samples with Nucleophiles.
Activated benzoquinone samples
(§S1.3.3) were washed with N,N-
dimethylformamide (ca. 20 mL),
blown dry under a stream of
argon and placed into a reaction tube containing either a) 3-azidopropylamine (0.1 M) in N,N-
dimethylformamide (10 mL) and catalytic amounts of 4-N,N-(dimethylamino)pyridine (see §S3,
SAM-4), or b) 2-(2-(2-methoxyethoxy)ethoxy)ethanamine 3 (0.1 M) in N,N-dimethylformamide
(1 mL) and 4-N,N-(dimethylamino)pyridine (2.0 mg, 0.02 mmol) to give SAM-3 (inset). The
reaction was continued in the dark at room temperature for 16 h and stopped by removing the
silicon wafer from the reaction mixture. Samples were washed with N,N-dimethylformamide,
ethanol and analyzed or further reacted.
S1.4 Benzoquinone Linker Reduction and Subsequent Release of Immobilized Species.
Electrochemical reduction22 of the benzoquinone linker moiety in the organic constructs SAM-3
allowed for a ‘trimethyl lock’-facilitated4 lactonization of the hydroquinone intermediate
(Scheme S1). The subsequent release immobilized species introduced on the benzoquinone acid
layer, aimed to reconstruct SAM-2, was monitored by spectroscopic methods (XPS and XRR),
contact angle goniometry and cell cultures experiments. Alternative reaction times, electrolyte
solutions and cathodic potentials were investigated for the ‘switch’ of a range of constructs.
S - 15 -

These findings are presented in a separate report. Only optimized ‘switch’ conditions are here
used for the electrochemical reduction of OEO-functionalized constructs (SAM-3). The
electrochemical removal of the anti-fouling OEO portion of the film and its effect on the
impaired ability of cultured cell to grow on the modified silicon substrate was investigated. The
anti-fouling OEO constructs were reductively converted to the cell-fouling lactonized precursor
(SAM-2) in DPBS (pH 7.4) applying cathodic bias (−1800 mV vs Ag|AgCl|3M NaCl) for 100 s
under ambient illumination and while keeping the system under an argon atmosphere. Samples
were then removed from the chamber, rinsed with copious amount of water and ethanol before
being used as substrates in cell culturing experiments.
S1.5 Surface Characterization
S1.5.1 Contact Angle Goniometry. Static water contact angles were measured with Ramé-Hart
200-F1 goniometer. Samples were prepared in triplicate with at least five separate spots being
measured for each sample. Contact angles were determined using a model derived from a first
order perturbation solution of the Laplace equation developed by Unser and co-workers.23
Tangent 2 fitting model. Reproducibility of these measurements was  3°.
S1.5.2 XPS Measurements. X-ray photoelectron spectroscopy experiments were used to
characterize surface modification steps and electrochemical cleaving experiments of Figure 1,
and were performed on an ESCALAB 220iXL spectrometer with a monochromatic Al Kα source
(1486.6 eV), hemispherical analyzer and multichannel detector (6 detectors). Spectra were
recorded in normal emission with the analyzing chamber operating below 10–8 Torr and selecting
a spot size of approximately 0.5 mm2. The incidence angle was set to 58˚ to the analyzer lens.
The resolution of the spectrometer is ca. 0.6 eV as measured from the Ag 3d5/2 signal (full width
at half maximum, fwhm) with a 20 eV pass energy. Survey scans were carried out over 1300−0
eV range with a 1.0 eV step size, a 100 ms dwell time and an analyzer pass energy of 100 eV.
High-resolution scans were run with 0.1 eV step size, dwell time of 100 ms and the analyzer pass
energy set to 20 eV.
After background subtraction using the Shirley routine, spectra were fitted with a convolution
of Lorentzian and Gaussian profiles as described previously. All energies are reported as binding
energies in eV and referenced to the C1s signal (corrected to 285.0 eV). When detected, the
fractional monolayer coverage of oxidized silicon was calculated directly from the oxidized/bulk
S - 16 -

Si 2p peak area ratio according to the method described by Webb and co-workers for very thin
oxide overlayers.24-25 According to this method, the spectrometer SiOx detection limit can be
approximated to ca. 0.06 ML equivalents.
The ratios of the integrated areas for the C 1s and N 1s emissions (C‒ C:N, carbon-bonded
carbons to total nitrogen), each normalized for their elemental sensitivity26, scanning time
(number of scans accumulated), and for a square root dependence on the photoelectron kinetic
energy, afforded an estimate of the conversion of the acetylenyl surface (SAM-1) to the lactone-
functionalized surface (SAM-2). Analogous quantitative considerations aided in understanding
the stoichiometry of the growing film, and partially allowed estimating reaction yields for the
assembly of SAM-3 and the outcome of its subsequent electrochemical cleaving processes.
S1.5.3 X-ray Reflectometry Measurements. X-ray reflectivity (XRR) spectra were used to
support the conversion of SAM-1 to SAM-3, and used to validate the electrochemical reduction
of the latter to its precursor surface (SAM-2). X-ray reflectivity profiles were measured in air on
a Panalytical Ltd X’Pert Pro reflectometer using Cu Kα X-ray radiation (λ = 1.54056 Å)
produced from a 45 kV tube source. The X-ray beam was focused using a Göbel mirror and
collimated with 0.1 mm pre- and post-sample slits. The reflected X-rays were counted using a
NaI scintillation detector. Reflectivity data were collected over the angular range 0.05   
5.00, with a step size of 0.010 and counting times of 10 s per step ( is the angle of incidence
of the X-ray beam impinging upon the surface). Samples had an average size of 10 × 30 mm.
Structural parameters of the prepared organic thin layers were refined using the MOTOFIT
reflectivity analysis software27 with reflectivity data as a function of the momentum transfer
vector Q (Q = 4π(sin)/λ). In the fitting routines the scattering length density of the silicon
substrate was held at 2.01 × 10−5 Å−2 and the Levenberg–Marquardt method was selected to
minimize χ2 values.28 Single-layer models were proposed when no significant improvement in
the fitting quality was observed upon the introduction of additional layer in the refined model.
All X-ray reflectivity curves were acquired in air for samples stored under an argon atmosphere
prior to analysis.
S1.5.4 Electrochemical Switch. All electrochemical measurements were performed using a
BAS 100B electrochemical analyzer (Bioanalytical Systems, Inc., W. Lafayette, IN) and a
conventional PTFE three-electrode cell as detailed previously.16 Electrolyte was DPBS (pH 7.4).
S - 17 -

Working electrodes had a geometric area of >350 mm2, with only a designated portion of it
(XRR: 30 × 10 mm; cell culturing experiments and XPS: 10 × 10 mm) immersed in the
electrolyte solution during electrode conditioning. Electrochemical experiments were conducted
in degassed (by means of bubbling argon gas for a minimum of 20 min) electrolytes.
S1.6 Cell Culturing Experiments
S1.6.1 Cell Culture. Aortic Endothelial Bovine cells (BAEC) were cultured in basal medium
Eagle (BME) supplemented with 10% fetal bovine serum at 37ºC at 5% CO2.
S1.6.2 Cell Adhesion Assay. Confluent (> 90% confluence) BAE cells were incubated in
glutamine-poor BME with 2% fetal bovine serum 12 h prior to cell adhesion experiments. Cells
were harvested with a trypsin solution in DPBS (0.02% w/v) and centrifuged. The supernatant
was removed and the cells (ca. 3 × 106 cells) were suspended in BME supplemented with serum
(8 mL). The cell suspension (1 mL) was added to the silicon sample (either SAM-3 or ‘switched’
samples) in a culture dish and cells were left to adhere at 37°C at 5% CO2. Approximately 30
min after plating the silicon samples were rinsed with DPBS solution (2 × 1 mL). Cells were
then fixed in ice-cold p-formaldehyde (4% v/v) for 10 min. Samples were rinsed with DPBS
solution (2 × 1 mL) before cells permeablized and blocked for 30 min in a saponin (0.1% w/v),
gelatine from cold water fish skin (0.2% w/v) and bovine serum albumin (0.5% w/v) solution in
DPBS (ca. 20 mL). Fixed and permeable cells were stained phalloidin conjugated to Alexa Fluor
555 (Molecular Probes) solution in a saponin (0.1% w/v), gelatine from cold water fish skin
(0.2% w/v) and bovine serum albumin (0.5% w/v) solution in DPBS (200 L). Staining was
performed at ambient temperature in the dark for 20 min before samples were rinsed with DPBS
solution (3 × 5 mL) and Milli-Q™ water (3 × 5 mL). Silicon samples were mounted onto a glass
cover slips using Mowiol (Calbiochem) mounting solution (ca. 50 L) and rested for 12 h at
room temperature shielded from the light.
S1.6.3 Fluorescence Microscopy Analysis and Cells Quantitation. Fluorescence images
were obtained on a Nikon Eclipse TE 2000-S epifluorescence microscope fitted with a mercury
arc lamp, Nikon G-2A filters (excitation 510–560 nm; emission 610 nm) equipped with an 60×
oil immersion and 20× dry objective lense. Images were processed with ImageJ 1.41o software
(Wayne Rasband, National Institutes of Health, USA). Cells with rounded morphology having
radius smaller then ca. 25 m were considered not adherent and not counted (e.g. Figure 4a). All
cells that spread and had actin stress fibres were considered adherent and therefore counted. A
S - 18 -

minimum of 5 fluorescence micrographs (20×) were acquired for each surface sample. A
minimum of 6 samples for each surface chemistry (SAM-3 and ‘switched’) were used for cell
culture experiments.
S2. Wet-chemistry Evidence for the Formation of Surface Assemblies Prepared from
Immobilized Lactones
As described in greater detail in § S1.3, NBS-promoted oxidation of the confined lactone
species 2 (SAM-2) was followed by carbodiimide/N-hydroxysuccinimide activation of the
putative benzoquinone acid product, and subsequent reaction with nucleophiles of interest (§
S1.3.4). The purpose of this section is two-fold: i) to provide “wet-chemistry” evidence for the
proposed conversion of a immobilized lactone moiety to the corresponding benzoquinone acid
upon its exposure to the oxidizing conditions investigated in the text; and ii) to provide
spectroscopic evidence for the lack of benzylic bromination upon aqueous NBS treatment.
Compound 4 was selected as a representative lactone derivative and used as starting material in
the wet-chemistry control experiments described below. The proposed synthetic scheme is
depicted in Scheme S4. Importantly, all spectroscopic data support the conversion of compound
4 to compound 4a upon treatment with aqueous NBS, with no evidence of brominated
byproducts. Further, formation of compound 4c is taken as supplementary evidence of the
formation of the putative azido-terminated construct as depicted in Figure S4.
Scheme S4. Ring-opening reaction on a representative solution phase system
i. NBS, 44%; ii. DCC/NHS, cat. DMAP, 45%; iii. NH2(CH2)3N3, DIPEA, 73%.
(i) 3-(2,5-Dimethyl-3,6-dioxocyclohexa-1,4-dienyl)-3-methylbutanoic acid (4a). To a stirred
solution of 6-hydroxy-4,4,5,8-tetramethylhydrocoumarin 4 (220 mg, 1.0 mmol) in water (0.4
mL) and acetonitrile (2.0 mL), N-bromosuccinimide (190 mg, 1.1 mmol) was added in 5
S - 19 -

portions. Stirring was continued at room temperature for 1 h. The reaction mixture was then
evaporated in vacuo and the oily residue extracted with dichloromethane (2 × 10 mL) after the
addition of water (5 mL). The crude material was purified by column chromatography
1
(dichloromethane) to give the title compound 4a as a yellow oil (105 mg, 44%). H NMR (300
MHz, CDCl3) : 5.59 (s, 1H), 2.56 (s, 2H), 2.41 (s, 3H), 2.37 (s, 3H), 1.46 (s, 6H); 13C NMR
(75.5 MHz, CDCl3) : 168.11, 147.41, 143.40, 130.77, 124.22, 120.68, 112.63, 45.86, 35.84,
27.61, 16.79, 15.36.
(ii)
2,5-Dioxopyrrolidin-1-yl-3-(2,5-dimethyl-3,6-dioxocyclohexa-1,4-dienyl)-3-
methylbutanoate, N-Hydroxysuccinimidyl ester (4b). To a stirred solution of 3-(2,5-dimethyl-3,6-
dioxocyclohexa-1,4-dienyl)-3-methylbutanoic acid 4a (70.0 mg, 0.30 mmol) in dry
dichloromethane (30 mL), N-hydroxysuccinimide (38.0 mg, 0.33 mmol), N,N'-
Dicyclohexylcarbodiimide (68.1 mg, 0.33 mmol) and 4-N,N-(dimethylamino)pyridine (2.0 mg,
0.02 mmol) were added in one portion. Stirring was continued at room temperature for 1 h under
an argon atmosphere. The reaction mixture was then cooled on an ice-water bath and filtered.
The filtrated was evaporated under reduced pressure and suspended in ice cold ethyl acetate (ca.
10 mL) before being filtered a second time. The filtrate was in vacuo and extracted with
dichloromethane (2 × 10 mL) from water (5 mL). The pooled organic phase was dried over
MgSO4, filtered and the solvent removed in vacuo pressure to afford the crude product as a
yellow oil. The crude material was crystallized in methanol at 4 ºC to afford the ester 4b as a
pale-yellow powder (45 mg, 45%).1H NMR (300 MHz, CDCl3) : 6.47 (s, 1H), 3.27 (s, 2H),
2.78 (s, 4H), 2.16 (s, 3H), 2.01 (s, 3H), 1.54 (s, 6H); 13C NMR (75.5 MHz, CDCl3) : 190.67,
187.32, 169.02, 167.78, 150.42, 148.13, 140.93, 131.77, 44.28, 39.32, 29.38, 25.68, 16.07, 14.17.
(iii)
N-(3-azidopropyl)-3-(2,5-dimethyl-3,6-dioxocyclohexa-1,4-dienyl)-3-methylbutanamide
(4c). To a solution of the N-hydroxysuccinimidyl ester 4b (30 mg, 0.09 mmol) in N,N-
dimethylformamide (5 mL), diisopropylethylamine (62 mg, 0.5 mmol ) and 3-azidopropylamine
(30 mg, 0.3 mmol) were added in one portion with stirring under an argon atmosphere. The
reaction mixture was heated at 50 ºC and stirring continued for an additional 16 h. The solution
was diluted with ethyl acetate (30 mL) and the crude mixture poured into a separatory funnel.
The organic phase was washed with brine (3 × 10 mL) and water (10 mL), dried over Na2SO4,
filtered and the solvent removed in vacuo. The crude was purified using column chromatography
1
(ethyl acetate/light petroleum, 2:1) to give the amide 4c as a yellow solid (21 mg, 73%). H
S - 20 -

NMR (300 MHz, CDCl3) : 6.47 (s, 1H), 3.26 (m, 4H), 2.87 (m, 1H), 2.30 (m, 7 H), 1.63 (bs,
13
1H), 1.23 (s, 3H), 1.12 (s, 3H), 0.84 (s, 3H). C NMR (75.5 MHz, CDCl3) : 196.80, 196.31,
174.63, 151.27, 138.88, 82.84, 50.33, 49.91, 46.73, 41.37, 40.17, 29.95, 27.21, 23.05, 16.68,
10.19. IR (KBr, cm−1): 3439, 2965, 2097, 1687, 1455, 1404, 1376, 1273.
S3. Reaction of NHS-Activated Samples with 3-Azidopropylamine
To aid in the study of the modular assembly and ‘switch’ strategy depicted in Figure 1, 3-
azidopropylamine was grafted onto the activated benzoquinone acid surface (§ S1.3.3). The
electron-deficient nitrogen atoms in azido groups of the putative surface product, is generally a
well resolved feature in N 1s XPS narrow scans with a ca. 3 eV separation from signals due to
nitrogen bonded to carbon.29-30
Figure S4 Wide XPS spectrograph of 3-azidopropylamine modified samples
Not easily distinguishable in the wide scan (Figure S4), but visible in high resolution N 1s
scans (Figure S5b), was a peak absent in the lactonized precursor (SAM-2) of mean binding
energy of 404.7 eV and resulting from electron-deficient nitrogen atoms in azido groups. This
finding was therefore consistent with a positive outcome of the immobilization of 3-
azidopropylamine. Curve fitting of the complex N 1s envelope was applied to support claims of
S - 21 -

Figure S5. High-resolution nitrogen 1s XPS spectrographs for (a) dormant redox linker in SAM-2, (b) azide-
decorated surface (SAM-4).
the product formation. The peak area ratio for the 405 eV curve (here referred to as N405) to the
main contribution in the ca. 399–402 eV region (simply indicated as N for clarity) was 0.7:6,
close to the stoichiometric ratio of 1:6 expected for an homogeneous array of surface bound
molecules. Non-quantitative yields for the stepwise procedure used in the construction of SAM-4
might account for the observed difference.
Despite all the chemical derivatization steps downstream from the passivation of the Si(100)
surface with diyne 1 being done in aqueous environments, and extensive handling of the samples
in air, either no or minor (ca. 0.06 SiOx fractional layers)24 silicon oxide related signals were
observed in the 102–104 eV region of the Si 2p XPS emission; again highlighting the
effectiveness of the base surface chemistry (i.e. SAM-1) in protecting the Si(100) surface from
oxidation. Sessile water contact angles values for SAM-4 were 58 ± 4º, a value close to those
reported for the lactonized surface (SAM-2) and did not afford supplementary information on the
surface chemistry.
As discussed above, the electron-deficient nitrogen atom (N405) of the terminal azide group of
SAM-4, with a well-resolved emission at 404.7 eV in the N 1s narrow scan (Figures S5b),
afforded a convenient XPS marker that facilitates deconvolution of experimental data.
A potential of −900 mV was applied to the silicon working electrode (SAM-4) for 300, 600
and 6000 s to reduce the quinone to the corresponding hydroquinone,31 which then could react
with the neighboring amide link and release 3-azidopropylamine. N 1s and Si 2p XPS
spectrographs for the electrochemically reduced substrates are shown in Figures S6 and S7,
respectively. Curve fitting of the complex N 1s envelope was applied to support claims of the
product formation. The observed N405:N peak area ratio decreased from 0.7:6, as for the
S - 22 -

untreated surface SAM-4, to ca. 0.5:6 for silicon samples reacted for either 300 s or 600 s at
−900 mV. As expected on the basis of molecular considerations, and as further supported by
Figure S6. XPS nitrogen 1s narrow scans for the electrochemical reduction (–900 mV) of construct SAM-4.
Spectrographs were acquired for silicon samples prior to (t = 0), and at defined time intervals (t = 300, 600 and 6000
s) during the cathodic lactonization process.
published data by Chidsey,29-30 azide on surfaces display a 1:2 peak area ratio for the N405:N
XPS signals, therefore simple algebraic considerations allowed to estimate a ca. 38% yield for
the electrochemical reduction of construct SAM-4 to surface SAM-2 upon the 10-min cathodic
‘switch’. Prolonged bias of SAM-4 (6000 s) were necessary to reduce the N405 emission to below
detectable levels, corresponding to a quantitative conversion to the final product. The
unexpectedly long polarization times required to complete the benzoquinone
reduction−hydroquinone lactonization sequence under this bias condition prompted the
investigation of more cathodic overpotentials for a rapid release of immobilized nucleophiles.
Optimized conditions are used in the ‘switch’ of the OEG –functionalized SAM-3 (main article).
Finding of this optimization study will be reported elsewhere.
Lack of significant signals corresponding to oxidized silicon atoms in Si 2p high-resolution
XPS spectrographs acquired at successive times during the reaction (Figure S7), indicated that
the overall SAM quality was not adversely affected by the electrochemical process performed in
aqueous systems.
S - 23 -

Figure S7. Si 2p region of XPS spectra for electrochemically cleaved construct SAM-4. Spectrographs were
acquired for samples prior to (t = 0), and at defined time intervals (t = 300, 600, and 6000 s) during the cathodic (–
900 mV) lactonization process.
S4. References
1.
nucleophilic displacement. J. Am. Chem. Soc. 1972, 94, (26), 9166-9174.
2. Amsberry, K.; Borchardt, R., Amine Prodrugs Which Utilize Hydroxy Amide Lactonization. I. A
Potential Redox-Sensitive Amide Prodrug. Pharm. Res. 1991, 8, (3), 323-330.
3. Wang, B.; Nicolaou, M. G.; Liu, S.; Borchardt, R. T., Structural analysis of a facile lactonization
system facilitated by a "trimethyl lock". Bioorg. Chem. 1996, 24, (1), 39-49.
4. Zheng, A.; Shan, D.; Wang, B., A Redox-Sensitive Resin Linker for the Solid Phase Synthesis of
C-Terminal Modified Peptides. J. Org. Chem. 1999, 64, (1), 156-161.
5. Rohde, R. D.; Agnew, H. D.; Yeo, W.-S.; Bailey, R. C.; Heath, J. R., A Non-Oxidative Approach
Borchardt, R. T.; Cohen, L. A., Stereopopulation control. II. Rate enhancement of intramolecular
toward Chemically and Electrochemically Functionalizing Si(111). J. Am. Chem. Soc. 2006, 128, (29),
9518-9525.
6.
Liotta, D.; Arbiser, J.; Short, J. W.; Saindane, M., Simple, inexpensive procedure for the large-
scale production of alkyl quinones. J. Org. Chem. 1983, 48, (17), 2932-2933.
7.
8.
Martin, O. M.; Mecozzi, S., Tetrahedron 2007, 63, 5539-5547.
Lewis acid promoted Claisen rearrangement (CR) was found to afford the product f in
satisfactory yields. Two alternative CR reaction conditions`, Method A and Method B`, were
investigated and failed to yield the rearranged product. Method A`; Compound e (30 mg`, 0.12 mmol)
was dissolved in 5 mL of a N`,N-dimethylformamide/N`,N-dimethylaniline (1:12) mixture and heated to
140 ºC with stirring for 2 h under argon. The solvent was removed under vacuum while heating the crude
mixture at 80 ºC. The obtained brown residue was dissolved in 50 mL of dichloromethane and washed
with 3 M HCl solution (2 × 30 mL). The organic phase was evaporated and the yellow oil obtained
characterized. No traces of rearranged product were found with the starting material recovered unaltered.
Method B`; Compound e (30 mg`, 0.12 mmol) was heated at 200 ºC under argon for 6 h. The crude
S - 24 -

mixture was diluted with dichloromethane and washed with brine. The organic solvent was evaporated in
vacuo and the brown residue purified via column chromatography (ethyl acetate/light petroleum`, 1:1) to
yield the unreacted starting material e and traces of the coumarin d.
9.
Clayden, J.; Greeves, N.; Warren, S.; Wothers, P., Organic Chemistry. Oxford University Press:
Oxford, 2001.
10.
Chemical oxidation of the confined lactone 2 leads to the exposure of a conveniently presented
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11.
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