Synthesis and applications of copillar[5]arene dithiols

Article abstract of DOI:10.1080/10610278.2015.1111375

A novel copillar[4+1]arene incorporating alkylthiol substituents was synthesised in three steps and structurally characterised as the first example of a pillar[n]arene to incorporate two terminal thiols on the same aromatic ring. The macrocycle was attach

Full text of DOI:10.1080/10610278.2015.1111375

Supramolecular Chemistry
ISSN: 1061-0278 (Print) 1029-0478 (Online) Journal homepage: http://www.tandfonline.com/loi/gsch20
Synthesis and applications of copillar[5]arene
dithiols
Raghuram Reddy Kothur, Flavia Fucassi, Gennaro Dichello, Ludovic Doudet,
Wafa Abdalaziz, Bhavik Anil Patel, Gareth W. V. Cave, Ian A. Gass, Dipak K.
Sarker, Sergey V. Mikhalovsky & Peter J. Cragg
To cite this article: Raghuram Reddy Kothur, Flavia Fucassi, Gennaro Dichello, Ludovic Doudet,
Wafa Abdalaziz, Bhavik Anil Patel, Gareth W. V. Cave, Ian A. Gass, Dipak K. Sarker, Sergey V.
Mikhalovsky & Peter J. Cragg (2015): Synthesis and applications of copillar[5]arene dithiols,
Supramolecular Chemistry, DOI: 10.1080/10610278.2015.1111375
To link to this article: http://dx.doi.org/10.1080/10610278.2015.1111375
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Date: 03 December 2015, At: 02:15

Supramolecular chemiStry, 2015
ꢁꢁꢂ://dx.dꢃꢄ.ꢃꢅg/10.1080/10610278.2015.1111375
ꢀ
Synthesis and applications of copillar[5]arene dithiols
a
a
a
a,b
a
Raghuram Reddy Kothur , Flavia Fucassi , Gennaro Dichello , Ludovic Doudet , Wafa Abdalaziz , Bhavik Anil
Patel , Gareth W. V. Cave , Ian A. Gass , Dipak K. Sarker , Sergey V. Mikhalovsky and Peter J. Cragga
a
c
a
a
a,d
ꢆ
b
Sꢇꢀꢃꢃꢈ ꢃf pꢀꢆꢅꢉꢆꢇꢊ ꢆnd Bꢄꢃꢉꢃꢈꢋꢇꢌꢈꢆꢅ Sꢇꢄꢋnꢇꢋs, unꢄvꢋꢅsꢄꢁꢊ ꢃf Bꢅꢄgꢀꢁꢃn, Bꢅꢄgꢀꢁꢃn, uK; eꢇꢃꢈꢋ Sꢌꢂéꢅꢄꢋꢌꢅꢋ dꢋ cꢀꢄꢉꢄꢋ oꢅgꢆnꢄqꢌꢋ ꢋꢁ mꢄnéꢅꢆꢈꢋ,
ꢇ
d
cꢃꢉꢂꢄègnꢋ, Fꢅꢆnꢇꢋ; Sꢇꢀꢃꢃꢈ ꢃf Sꢇꢄꢋnꢇꢋ & tꢋꢇꢀnꢃꢈꢃgꢊ, Nꢃꢁꢁꢄngꢀꢆꢉ tꢅꢋnꢁ unꢄvꢋꢅsꢄꢁꢊ, Nꢃꢁꢁꢄngꢀꢆꢉ, uK; Nꢆzꢆꢅbꢆꢊꢋv unꢄvꢋꢅsꢄꢁꢊ, asꢁꢆnꢆ, Kꢆzꢆkꢀsꢁꢆn
ABSTRACT
ARTICLE HISTORY
A novel copillar[4+1]arene incorporating alkylthiol substituents was synthesised in three steps and
structurally characterised as the first example of a pillar[n]arene to incorporate two terminal thiols
on the same aromatic ring. The macrocycle was attached to gold electrodes through a standard
rꢋꢇꢋꢄvꢋd 4 Sꢋꢂꢁꢋꢉbꢋꢅ2015
aꢇꢇꢋꢂꢁꢋd 16 oꢇꢁꢃbꢋꢅ2015
KEYWORDS
+
dipping technique. Cyclic voltammetry demonstrated selectivity for Li over other alkali metal
pꢄꢈꢈꢆꢅ[5]ꢆꢅꢋnꢋs; ꢉꢆꢇꢅꢃꢇꢊꢇꢈꢋs;
gꢃꢈd nꢆnꢃꢂꢆꢅꢁꢄꢇꢈꢋs; sꢌꢅfꢆꢇꢋ
ꢉꢃdꢄfiꢇꢆꢁꢄꢃn
cations. The copillar[4+1]arene was also used as a capping agent in the preparation of 3 nm gold
nanoparticles.
1
. Introduction
molecules. The simplest derivative, 1,4-DMP[5]A, even
without further functionalisation, can be used as an elec-
trode modifier to detect Na across the entire physiological
Pillar[5]arenes are macrocycles belonging to the broad
class of cyclophanes and are comprised of five aromatic
rings linked by methylene bridges in the 2,5-positions with
O-alkyl substituents in the 1,4-positions. The first exam-
ple, 1,4-dimethoxypillar[5]arene (1,4-DMP[5]A, 1), was
reported in 2008 (1). Many other derivatives have since
been prepared and shown to have a range of interesting
properties from recognition of linear alkyl diamines to
the formation of channels that act as conduits for protons
+
range (12).
It is possible to introduce different groups during the
initial macrocyclisation by using two monomers to form so
called‘copillar[5]arenes’that incorporate the monomer in
a 4:1 ratio (copillar[4+1]arene) or a 3:2 ratio (copillar[3+2]
arene) (13, 14). Other reactions of monomers leading to
copillar[2+3]arene and copillar[1+4]arene are theoreti-
cally possible although, to date, the focus has been on
the higher yielding [4+1] and [3+2] derivatives (Scheme 1).
Copillar[5]arenes such as 2 and 3 (Figure 1) can undergo
further reactions so that functional groups can be intro-
duced as in dithiol 4. An alternative stratagem involves
(2–11). The cyclopentameric macrocycles are tubular, with
a central cavity approximately 4.7 Å wide by 7.8 Å long
for 1,4-DMP[5]A, possessing D symmetry and have been
shown to act as hosts for a range of neutral and charged
chemical guests (3). The rings of oxygen atoms at each
orifice provide good binding sites for guest species such
as metal cations, planar aromatic species and linear alkyl
5h
partial or total demethylation of 1 with BBr followed by
3
the reduction of the resulting quinones to phenols by
CONTACT pꢋꢁꢋꢅ J. cꢅꢆgg
p.J.cꢅꢆgg@bꢅꢄgꢀꢁꢃn.ꢆꢇ.ꢌk
©
2015 tꢆꢊꢈꢃꢅ & Fꢅꢆnꢇꢄs

2
R. R. KOTꢀꢁR ꢂT AL.
nanoparticle capping agents or for surface functionalisa-
tion can be found in the work of Li (20), Diao (21), and Jia
(22). In these cases, the pillar[5]arene attaches to the metal
surface through one of its functionalised rims. This results
in the nanoparticles being covered in macrocyclic recep-
tors that can be exploited to respond to particular guest
molecules. For example, Zhou treated sodium citrate sta-
bilised AuNPs with monothiolated derivative, 7, and was
able to demonstrate attachment through a combination
of Fourier transform infrared (FTIR) and ꢁV–vis spectros-
copy (23). The modified AuNPs reversibly assembled as a
consequence of the photocycloaddition of anthracene
guest species. Other applications of pillar[n]arene-coated
nanoparticles include pillar[5]- and [6]arene-capped nan-
oparticles to detect alkylpolyamines (24), hybrid AuNPs
that form from responsive pillar[5]arene-containing poly-
mers (25), carboxylated pillar[5]arene-coated AuNPs with
peroxidase activity (26), pꢀ- and NIR-triggered controlled
release by pillar[6]arene-modified AuNPs and nanorods
Scheme 1. (cꢃꢈꢃꢌꢅ ꢃnꢈꢄnꢋ) cꢃꢂꢄꢈꢈꢆꢅ[5]ꢆꢅꢋnꢋ sꢊnꢁꢀꢋsꢄs.
(27) and the use of cationic pillar[5]arene-coated AuNPs
to detect pyrene by surface-enhanced Raman scattering
spectroscopy (28).
In our pillar[5]arene-based cation (12) and pꢀ sensors
(11), the guest species are able to enter the macrocycle
from either end and be trapped within the central aromatic
annulus. ꢂxamples such as Stoddart’s fluorescent copil-
lar[5]arene (9) demonstrate that it is important for linear
guests to thread through the macrocycle in order to differ-
entiate between alkyl amines and diamines with varying
lengths and distances between amine groups. The same
phenomenon has since used to form pseudorotaxanes
(29–33) and, in an elegant extension of this, to synthesise
a [1]rotaxane (34). We wished to broaden the application of
this threading mechanism to develop pillar[5]arene-based
sensors, such as gold microelectrodes and acoustic wave
sensors, where the macrocycles are covalently bound to
surfaces and respond to changes electrical conductance
upon guest binding. To achieve this, a thiol derivative of
pillar[5]arene seemed appropriate due to the well-known
affinity of sulfur for gold. Indeed, the same idea under-
pinned Zhou’s synthesis and use of 7 as a capping agent
for AuNPs. The strategy that we adopted was to use copil-
lar[5]arene precursors that allow thiols to be introduced
in the 1,4-positions of one or two aromatic moieties of a
copillar[4+1]arene or copillar[3+2]arene. In particular, we
aimed to synthesise a copillar[4+1]arene with only two
thiols, both on the same ring, so that when it was attached
to a gold surface the cavity of the copillar[4+1]arene would
lie parallel, rather than perpendicular, to the surface and
allow guests to pass through this channel. We also required
short linkers between the pillar[5]arene and the terminal
thiols to bind the macrocycle close to the gold surface so
that, in the case of electrochemical applications, the effect
Figure 1. (cꢃꢈꢃꢌꢅ ꢃnꢈꢄnꢋ) cꢃꢂꢄꢈꢈꢆꢅ[5]ꢆꢅꢋnꢋs dꢋsꢇꢅꢄbꢋd ꢄn ꢁꢀꢋ ꢁꢋxꢁ.
sodium dithionite (15). O-Alkylation can then be used to
introduce a range of substituents (16).
Recently, several groups have employed pillar[5]arenes
in the synthesis of functionalised nanoparticles prepared
from gold (AuNPs) and silver (AgNPs). The imidazolium
derivative, 5, was shown by ꢀuang to promote the forma-
tion of AuNPs from ꢀAuCl in aqueous solution following
4
the addition of NaBꢀ with sizes controlled by the con-
4
centration of pillar[5]arene added (17). The carboxylate
derivative, 6, was employed by Yang and Weiss to prepare
AuNPs. They proposed that strong carboxyl-gold-binding
interactions stabilised the AuNPs during their formation
and that, furthermore, growth of the AuNPs during the
reduction step was suppressed (18). Compound 6 has
also been shown by Xue to control the size of AgNPs (19).
Other examples where pillar[n]arenes have been used as

SꢁPRAMOLꢂCꢁLAR CꢀꢂMISTRY
3
was used to displace tetracoctylammonium bromide to
stabilise AuNPs resulting in particles with a diameter of
2
.9 ± 0.9 nm.
2
. Results and discussion
.1. Copillar[4+1]- and [3+2]arene dithiol synthesis
sing ꢀuang’s method, 1,4-bis(bromoethoxy)benzene
2
ꢁ
was prepared in 80% yield from 1,4-bis(hydroxyethoxy)
benzene (17). It was noticeable that both the yield and
purity of the product were reduced if powdered, rather
than crystalline, 1,4-bis(hydroxyethoxy)benzene was used.
The alkyl bromide copillar[4+1]- and [3+2]arenes were pre-
pared using Meier’s iron-catalysed method (35) to give 2
and 3 which were isolated in 33 and 10% yields, respec-
tively, following column chromatography. ꢁsing other
reaction conditions, we have seen mass spectrometric
evidence for [2+3] and [1+4] regioisomers but they were
not observed under these conditions. The yield of 2 com-
pares favourably with the 19% reported by Zhang and
Yang for the same copillar[4+1]arene prepared with trifluo-
romethanesulfonic acid as the catalyst (36). An alternative
approach using BF ∙O(C ꢀ ) in dry 1,2-dichloroethane was
Figure 2. (cꢃꢈꢃꢌꢅ ꢃnꢈꢄnꢋ) X-ꢅꢆꢊ sꢁꢅꢌꢇꢁꢌꢅꢋ ꢃf 2·DmF·0.5 h2o
ꢀꢊdꢅꢃgꢋn ꢆꢁꢃꢉs ꢅꢋꢉꢃvꢋd fꢃꢅ ꢇꢈꢆꢅꢄꢁꢊ).
(
3
2 5 2
attempted but the yield of 2 was only 18%. No formation
of 3 was observed by this method (see Supplementary
Information). ꢁsing the low temperature approach of ꢀu
and Fox (37), compound 2 was treated with hexamethyld-
isilathiane to give dithiol 4 in 85% yield.
2
.2. X-ray crystallography
Derivatives 2 and 3 could be crystallised from meth-
anol:DMF (1:1). The single crystal X-ray structure of 2
showed that it crystallises as the DMF solvate with a single
solvent guest in the macrocyclic cavity. The structure was
solved in the P2 /n space group with one bromine atom
1
disordered over two sites, with occupancies of 92 and
8
%, and a water molecule modelled at 50% occupancy.
Simple pillar[5]arenes crystallise out in racemic planar chi-
ral forms and consequently the unit cell of 2 contains two
molecules with Sp and two with Rp chirality. For simplicity,
only the Rp form is illustrated in Figure 2. The structure
of copillar[5]arene 3 was problematic to solve and could
only be resolved as a 4:1 cocrystallised mixture of 3·DMF
and 2·DMF·Cꢀ Cl . Cocrystallisation is consistent with the
Figure 3. cꢊꢇꢈꢄꢇ vꢃꢈꢁꢆꢉꢉꢋꢁꢅꢊ dꢌꢅꢄng ꢇꢃꢂꢄꢈꢈꢆꢅ[4+1]ꢆꢅꢋnꢋ
ꢆꢁꢁꢆꢇꢀꢉꢋnꢁ: (ꢆ) ꢁꢀꢋ ꢋffꢋꢇꢁ ꢃf ꢆꢁꢁꢆꢇꢀꢉꢋnꢁ ꢁꢄꢉꢋ wꢄꢁꢀ 4 ꢃn ꢆ gꢃꢈd
ꢋꢈꢋꢇꢁꢅꢃdꢋ ꢆnd (b) ꢁꢀꢋ ꢃxꢄdꢆꢁꢄꢃn ꢂꢋꢆk ꢇꢌꢅꢅꢋnꢁ dꢋꢇꢅꢋꢆsꢋ wꢄꢁꢀ ꢁꢄꢉꢋ
(
0.01 m K [Fꢋ(cN) ] ꢄn 0.1 m hcꢈ sꢌꢂꢂꢃꢅꢁꢄng ꢋꢈꢋꢇꢁꢅꢃꢈꢊꢁꢋ).
4 6
of guest inclusion could be transmitted directly to the
electrode. By contrast, Zhou’s monothiol has a single four
carbon spacer which allows the macrocycle to lie further
from the metal surface which is ideal for the promotion of
particle aggregation but less amenable to electrochemi-
cal guest detection. As proof of principle, 4 was attached
to a gold electrode and demonstrated a selectivity for Li+
over other alkali metal cations. To investigate whether the
derivative could have applications in AuNP chemistry, 4
2
2
appearance of both 2 and 3 in the mass spectrum of chro-
matographic fractions that gave an apparent single spot
by TLC. The structure could not be resolved satisfactorily
however, although the R-factor was 9.87%, the connectiv-
ity is unequivocal and shows –Cꢀ Cꢀ Br substituents on
2
2
the A and C rings, not the A and B rings, in agreement with
NMR data (see Supplementary Information). Furthermore,
the crystal structure indicates that the macrocycles are in

4
R. R. KOTꢀꢁR ꢂT AL.
the presence of these cations, significant differences in
+
+
+
the capacitive signal were observed for Li , Na , and K
+
salts with the greatest reduction was observed for Li .
Although not statistically significant, some reduction in
the capacitive signal was also observed with Rb and Cs .
The decrease in the capacitance is due to changes in the
double layer in the vicinity of the electrode which alters
+
+
+
the capacitive current at the electrode surface. If Li is held
within the pillar[5]arene the electrode surface is less acces-
sible to the free ions in solution, which are repelled, thus
the double-layer profile is influenced and the net capaci-
tance is reduced. The electrochemical response follows the
unusual ꢂisenman sequence XI in which transport follows
Figure 4. cꢀꢆngꢋs ꢃbsꢋꢅvꢋd ꢄn ꢁꢀꢋ ꢇꢆꢂꢆꢇꢄꢁꢆnꢇꢋ sꢄgnꢆꢈ ꢃn bꢆꢅꢋ
gꢃꢈd ꢋꢈꢋꢇꢁꢅꢃdꢋs ꢆnd gꢃꢈd ꢋꢈꢋꢇꢁꢅꢃdꢋs ꢇꢃꢆꢁꢋd wꢄꢁꢀ 4 (dꢆꢁꢆ sꢀꢃwn ꢆs
ꢉꢋꢆn ± sꢁ. dꢋv., wꢀꢋꢅꢋ *p < 0.05, **p < 0.05 ꢆnd ***p < 0.001 vs.
+
+
+
+
+
the order of ionic radii (Li > Na > K > Rb > Cs ) rather
than the order of dehydration (38). In previous work on
pillar[5]arene immobilised in composite electrodes, we
ꢁꢀꢋ bꢆꢅꢋ gꢃꢈd ꢋꢈꢋꢇꢁꢅꢃdꢋ).
the expected pseudo-D5h geometry observed for other
alkylated pillar[5]arene derivatives.
+
+
have seen that Rb and Cs are excluded from the pillar[5]
+
arene cavity based on their ionic radii, K binds strongly,
+
+
Na binds reversibly and Li does not bind at all (12). We
ascribed the selectivity to a combination of cation size and
complementarity to the cavity of the pillar[5]arene when
locked into a rigid pentagonal geometry. When the mac-
rocycle is attached to a surface through substituents on
one aromatic ring, as is the case for 4, the remaining rings
are free to change conformation. They can therefore adopt
the coordination geometry preferred by each cation. As a
2
.3. Electrode modification
Cyclic voltammetry was used to determine whether 4
could be successfully attached to gold electrodes and
function as an electrode modifier. The standard dipping
method was adopted to attach 4 to the surface of a gold
electrode and cyclic voltammograms of the redox couples
of K [Fe(CN) ] before and during the process were com-
pared (Figure 3). Both the capacitive and faradic current
were attenuated with increasing time (Figure 3(a)), con-
sistent with a coating of the macrocycle on the conductive
gold surface. After 4 h, no significant oxidation or reduc-
tion peak current for K [Fe(CN) ] was observed on the gold
4
6
+
consequence, Li could be bound effectively without the
need to be completely dehydrated which is energetically
unfavourable. This is consistent with the observations
of Shurpik who reported the binding constants for the
+
+
+
+
Li , Na , K , and Cs with 8, 9, and 10 in methanol. In all
4
6
+
cases log Kass was highest for Li over the other cations
electrode, suggestive of maximum coverage by 4 within
this time (Figure 3(b)).
(
39). Selectivity for the lightest alkali metal is of note as
+
Li detection remains a challenge in analytical chemistry.
2
.4. Assessment of copillar[4+1]arene-coated gold
2
.5. Preparation of copillar[4+1]arene-coated gold
electrodes for alkali metal detection
nanoparticles
Figure 4 shows how the capacitive responses varied for
bare gold electrodes and gold electrodes coated with 4.
Cyclic voltammetry was utilised to characterise the capac-
itive signal on 10 mM solutions of alkali metal cations. In
As an indication of the range of analytical methods that
could benefit from thiol-substituted 4, AuNPs were pre-
pared using the Brust–Schiffrin method (40) as modified
Figure 5. aꢌNps ꢇꢆꢂꢂꢋd bꢊ 4. (ꢆ)–(ꢇ) sꢀꢃw tem ꢄꢉꢆgꢋs ꢆnd (d) ꢆ fꢅꢋqꢌꢋnꢇꢊ ꢀꢄsꢁꢃgꢅꢆꢉ.

SꢁPRAMOLꢂCꢁLAR CꢀꢂMISTRY
5
by Katz for use with mercaptocalixarenes (41). Analysis of
transmission electron microscopy (TꢂM) images (Figure 5)
revealed that the AuNPs capped by 4 were 2.9 ± 0.9 nm in
diameter, similar in size to those prepared from 6 by Yang
and Weiss (3.1 ± 0.5 nm) (18). AuNPs prepared without 4
exhibited a broad distribution from 1 to 6 nm indicating
that the pillar[4+1]arene is able to control particle size (see
Supplementary Information).
Cꢀ instruments software. X-ray data were collected on a
Bruker X8 Apex II CCD diffractometer using a MoK radia-
α
tion source (λ = 0.71073 Å).
4
.1. Ligand synthesis
1,4-Bis(bromoethoxy)benzene
1,4-Bis(hydroxyethoxy)benzene (5.00 g, 25.2 mmol) and
triphenylphosphine (15.00 g, 60 mmol) were stirred in
Cꢀ CN and cooled to 0 °C. Carbon tetrabromide (20.00 g,
3
3
. Conclusions
6
0 mmol) was slowly added in small portions to a solu-
A novel copillar[4+1]arene derivative has been synthesised
and attached to the gold surfaces of electrodes. It has also
been used as a capping agent to prepare gold nanoparti-
cles. ꢁnlike other examples where pillar[5]arenes interact
through substituents at one end of the macrocyclic cavity,
attachment to a gold surface by two thiol groups allows 4
to lie parallel to the surface so that guest species can pass
through. The electrochemical response to alkali metal salts
tion with stirring while maintaining 0 °C. The reaction mix-
ture was then left to warm to room temperature and the
resulting clear solution was stirred for a further 4 h under
a nitrogen atmosphere. Cold distilled water (100 ml) was
added to precipitate a white solid that was collected by
vacuum filtration and recrystallised from hot methanol
(200 mL). 1,4-Bis(bromoethoxy)benzene was isolated as
white flake-like crystals following vacuum filtration. Yield:
+
1
by 4 indicates selectivity for Li over the other cations.
6.54 g (80%); m.p.: 112.7–115.6 °C; ꢀ NMR (400 Mꢀz,
CDCl ) δ (ppm): 6.85 (s, 4ꢀ, ArH), 4.23 (t, 4ꢀ, −CH O), 3.59
3
2
1
3
(
1
t, 4ꢀ, −CH Br); C NMR (90 Mꢀz, CDCl ) δ (ppm): 152.89,
2
3
4
. Experimental
16.17, 68.81, 29.19. ꢀRMS (m/z): calcd for C ꢀ Br O ·Na
10 12 2 2
All chemicals, solvents and reagents were purchased
commercially and used without further purification.
All solvents used were of at least reagent plus grade
C ꢀO , 391.9063; found, 391.9195. Note: the molecular ion
could not be detected for this compound and was always
observed as the sodium orthoformate complex.
2 2
(
>98.5%). Compounds were synthesised according to the
literature with amendments as described. For nanopar-
ticle synthesis, hydrogen tetrachloroaurate(III) trihydrate
1,4-Bis(bromoethyoxy)copillar[5]arenes
1,4-Dimethoxybenzene (11.96 g, 86.56 mmol) and
1,4-bis(bromoethoxy)benzene (1.75 g, 5.41 mmol) were
dissolved in dry Cꢀ Cl (350 mL). Paraformaldehyde
(
(
(
ꢀAuCl ·3ꢀ O, 99.9%), tetraoctylammonium bromide
4 2
+
−
TOAB, [Cꢀ (Cꢀ ) ] N Br , >98%) and sodium borohydride
3
2 7 4
2
2
NaBꢀ >98%) were purchased from Sigma-Aldrich. TꢂM
(7.80 g, 259.68 mmol) was added and the mixture sirred
under a nitrogen atmosphere. After cooling to 0 °C, FeCl3
(2.19 g, 13.53 mmol) was added with stirring. The temper-
ature was maintained at 0 °C for a further 30 min, during
which time the solution turned light green, before being
allowed to warm to room temperature, whereupon it was
stirred for a further 3 h, turning dark green in the process.
After completion of the reaction, distilled water (100 mL)
was added. The organic layer was isolated, washed with
distilled water (100 mL), saturated brine (100 mL) and
dried over Na SO . After filtration the solvent was removed
4
images of AuNPs were collected on a ꢀitachi-7100 Gatan
ltrascan 1000 CCD camera at 100 kV accelerating volt-
ꢁ
age. Compounds were characterised by NMR and infra-
red spectroscopy, melting point and high-resolution mass
spectrometry (ꢀRMS) to confirm their identities. NMR data
were collected by a Bruker Avance DMX-400 spectrometer
1
13
at 400 Mꢀz for ꢀ and 90 Mꢀz for C with tetramethylsi-
lane (TMS) as the internal reference. Chemical shifts are
reported in parts per million (ppm) downfield from TMS
1
(
0 ppm) as the internal standard. Multiplicities in the ꢀ
2
4
NMR spectra are reported as (s) singlet, (d) doublet and (t)
triplet. ꢂlectrospray ionisation mass spectra were recorded
by a Bruker Daltonics microTOF spectrometer operating
in the positive mode. Infrared absorption spectra were
recorded on a Nicolet Avatar 320 FT-IR fitted with a Smart
Golden Gate®. Melting points were determined on a BI
Barnstead ꢂlectrothermal Ltd melting point apparatus and
are uncorrected. Gold electrodes (3.0 mm diameter) were
mechanically polished and coated with a self-assembled
monolayer of copillar[4+1]arene 4. ꢂlectrochemical data
were collected with an Ag/AgCl reference electrode using
under vacuum and purified by column chromatography
(silica, 230–400 mesh, 3.0 cm × 25.5 cm column), using a
mixture of petroleum ether and Cꢀ Cl (initially 2:1 then
decreasing to 1:1) as the eluent. Two products (2 and 3)
were obtained as white solids.
2
2
1,4-Bis(bromoethyoxy)copillar[4+1]arene (2): yield
1.56 g (33%); R : 0.66 (petroleum ether:Cꢀ Cl 1:1; silica
f
2
2
1
40–70 Å); m.p.: 127.5 °C; ꢀ NMR (400 Mꢀz, CDCl ) δ (ppm):
3
6.79 (d, J = 5.6 ꢀz, 4ꢀ, −ArH), 6.77 (s, 4ꢀ, −ArH), 6.73 (s, 2ꢀ,
−Arꢀ), 4.06 (t, J = 6.2 ꢀz, 4ꢀ, CH O), 3.79 (s, 4ꢀ, ArCH Ar),
2
2
3.78 (s, 6ꢀ, ArCH Ar), 3.69 (s, 18ꢀ, OCH ), 3.74 (s, 6ꢀ, OCH ),
2
3
3

6
R. R. KOTꢀꢁR ꢂT AL.
1
3
3
1
1
5
2
.55 (t, 4ꢀ, −CH Br); C NMR (90 Mꢀz, CDCl ) δ (ppm):
subsequently discarded to leave gold(III) in toluene solu-
tion. Compound 4 (6.4 mg, 6.8 μmol, equivalent to a thiol
concentration of 0.14 mM) was added to the mixture with
vigorous stirring which was continued for a further 30 min.
2
3
50.85, 150.78, 150.74, 149.74, 129.11, 128.57, 128.24,
28.15, 127.82, 115.83, 114.39, 114.03, 113.93, 68.74, 56.05,
5.82, 55.79, 55.76, 34.00, 29.88, 29.80, 29.56; IR (ν, cm ):
929.4, 2100.2, 1721.4, 852.2, 696.4; ꢀRMS (m/z): calcd for
−1
Freshly prepared aqueous 0.4 M NaBꢀ (0.5 mL, 7.44 mg,
4
C ꢀ Br NaO , 959.1804; found, 959.2048. Data are in
10 equiv.) was added dropwise at a rate of approximately
20 μl every 15 s with vigorous stirring. The gold(III) solution
turned brown over 90 s whereupon the remainder of the
4
7
52
2
10
agreement with literature values (36).
,4-Bis(bromoethyoxy)copillar[3+2]arene (3): yield:
07 mg (10%); R : 0.80 (petroleum ether:Cꢀ Cl 1:1; sil-
1
6
NaBꢀ solution was added. The mixture was stirred for 4 h
f
2
2
4
1
ica 40–70 Å); m.p.: 140.24 °C; ꢀ NMR (400 Mꢀz, CDCl )
and the aqueous phase was subsequently discarded. The
final toluene solution (10 mL) contained ~0.2 mM of gold
and 40 mM of TOAB and was stored in a glass container in
the dark for characterisation using ꢁV–vis spectroscopy
and TꢂM. A control experiment was carried out using the
same procedure but in the absence of 4. FTIR following the
attachment of 4 showed the characteristic absorbance at
3
δ (ppm): 6.90−6.91 (m, 6ꢀ, −Arꢀ), 6.85 (d, 4ꢀ, −Arꢀ),
3
−
.93−3.97 (m, 8ꢀ, ArCꢀ Ar), 3.78−3.81 (m, 28ꢀ, ArCꢀ Ar+
2
2
1
3
OCꢀ ), 3.49−3.52 (m, 8ꢀ, −Cꢀ Br); C NMR (90 Mꢀz,
3
2
CDCl ) δ (ppm): 150.82, 150.80, 150.73, 149.73, 129.26,
3
128.55, 127.95, 115.78, 115.73, 114.34, 113.92, 68.83, 68.74,
5
6.05, 55.79, 39.7, 31.84, 31.53, 29.95, 29.67, 29.59, 28.97;
−
1
−1
IR (ν, cm ): 2932.1, 1910.2, 1781.2, 1730.3, 850.1, 692.3;
RMS (m/z): calcd for C ꢀ Br NaO , 1145.0308; found,
3200 and 1600 cm indicative of aromatic compounds
ꢀ
and used by Zhou to prove attachment of 7 to AuNPs (23)
(supplementary information, Figure S10). ꢁV–vis scans of
the AuNPs show subtle changes around 520 nm which
indicate that replacement of TOAB by 4 though the peaks
are too broad to be used to extrapolate changes in AuNP
sizes as a consequence of TOAB replacement (supplemen-
tary information, Figure S11).
4
9
54
4
10
1144.9071.
1
,4-Bis(thioethyoxy)copillar[4+1]arene
1,4-Bis(bromoethoxy)copillar[4+1]arene (2) (0.200 g,
0.213 mmol) was dissolved in dry TꢀF (10 mL) at −30 °C
under nitrogen. S(SiMe3)2 (0.09 mL, 0.426 mmol) and
tetrabutylammonium fluoride trihydrate (TBAF·3ꢀ O)
2
(
0.296 g, 0.941 mmol) were added and the resulting light
4
.3. Attachment of copillar[4+1]arenes to gold
green reaction mixture was stirred overnight and allowed
to warm to room temperature. TꢀF was removed under
vacuum from the resulting colourless mixture and a mix-
ture of distilled water (20 mL) and Cꢀ Cl (20 mL) were
added. The organic layer was isolated and washed with
distilled water (3 mL × 20 mL). The organic layer was dried
with Na SO , filtered, and the solvent removed under
electrodes
The gold electrode (2.0 mm diameter) was mechanically
polished with two micropolish alumina suspensions of 0.3
and 0.5 μ, respectively, for 3 min each and washed with
distilled water. Subsequent ultrasonic cleaning with abso-
lute ethanol removed the residual alumina powder. After
mechanical cleaning, the gold electrode was immersed in
piranha solution (ꢀ SO /ꢀ O , 1:3 v/v) for 10 min at room
2
2
2
4
vacuum to give the crude product as a pale yellow solid.
Recrystallisation from methanol gave 1,4-bis(thioethyoxy)
2
4
2
2
copillar[4+1]arene (4) as a pale yellow solid. Yield: 155 mg
temperature and finally washed with distilled water. Prior
to sensor fabrication, a gold working electrodes was elec-
trochemically cleaned by cycling between −0.3 and 1.5 V
at a scan rate 0.1 V s vs. Ag|AgCl in 0.5 M sulfuric acid until
gold oxide formation was detected in the voltammogram.
The electrodes were washed thoroughly with distilled
water and dried in a nitrogen stream to obtain a clean
gold surface. The modified electrodes were characterised
by cyclic voltammetry. All cyclic voltammetric measure-
ments were taken using of Ag|AgCl as a reference elec-
trode and platinum wire as a counter electrode. A solution
of 10 mM K [Fe(CN) in 1 M KCl (pꢀ 7.0) was used as a redox
1
(
(
85%); m.p.: 188.0–192.0 °C; ꢀ NMR (400 Mꢀz, CDCl ) δ
3
ppm): 6.77–6.73 (m, 10ꢀ, −ArH), 4.12 (t, 4ꢀ, −CH O), 3.77 (s,
2
1
1
1
5
1
8
0ꢀ, ArCH Ar), 3.65 (d, 24ꢀ, −OCH ), 3.02 (m, 4ꢀ, −CH Sꢀ),
2 3 2
13
.42 (m, 2ꢀ, −SH); C NMR (90 Mꢀz, CDCl ) δ (ppm): 150.93,
3
50.87, 128.66, 128.44, 128.20, 114.39, 114.23, 65.79, 56.06,
−1
5.91, 55.84, 50.80, 29.73, 15.23. IR (ν, cm ): 2930.3, 1497.3,
397.5, 1272.6, 908.3, ꢀRMS (m/z): calcd for C ꢀ NaO S ,
47
54
10 2
65.3056; found, 865.3141.
4
.2. Nanoparticle synthesis
4
6
−1
Direct synthesis of AuNPs was based on a modification of
probe and scanned at 0.1 V s from −0.2 to +0.6 V.
a previously reported method (32). ꢀAuCl ·3ꢀ O (7.75 mg,
ꢂlectrode modification was carried out in a glass tube,
where only the gold surface was in contact with organic
reagent. The gold electrode was dipped in a solution of 4
(20 mg in 2 mL TꢀF) for varying durations (20 min to 6 h) at
ambient temperature before being washed several times
4
2
19.7 μmol) was dissolved in distilled water (0.7 mL) and
added immediately to TOAB (10 mL, 0.215 g, 20 equiv.)
dissolved in toluene. The biphasic mixture was stirred
for 30 min at room temperature and the aqueous phase

SꢁPRAMOLꢂCꢁLAR CꢀꢂMISTRY
7
with pure ethanol and then with double-distilled water.
The modified gold electrodes were kept in double-distilled
water.
completeness = 85.8% (2θ = 58.8°), 97.3% (2θ = 55°), R1
(I > 2σ(I)) = 0.0750, wR (I > 2σ(I)) = 0.1652, R = 0.1550,
2
1
wR (all data) = 0.2117. GOF = 1.027 for 606 parameters
2
and 0 restraints, largest diff. peak and hole 0.849/−1.023
3
eǺ . CCDC: 1404413.
4
.4. Surface analysis
Attachment of 4 to gold electrodes was assumed to be
complete after 4 h as shown in Figure 3(b) as no further
changes in peak current were observed. To confirm this,
unmodified and modified electrodes were imaged by SꢂM
and surface composition determined by energy disper-
sive X-ray spectroscopy (ꢂDX). SꢂM images show a broadly
smooth gold surface, with a little pitting, which becomes
uniformly uneven following addition of 4 (Supplemental
material, Figure S12). No sulfur is evident on the surface
prior to attachment of 4 but ꢂDX shows it to be present
after addition. The theoretical ratio of carbon to sulfur in 4
is 1:0.114; the ratio from ꢂDX is 1.00 (±0.024):0.095 (±0.03)
which falls within the expected range and proves that 4
has bound to the electrode surface.
Supplemental material
Supplemental data for this article can be accessed here: http://
dx.doi.org/10.1080/10610278.2015.1111375
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by the BBSRC under [grant number
BB/K013807/1]; the MRC under [grant number MR/J006661/1];
and the ꢁniversity of Brighton through a ꢁniversity Studentship
to RRK.
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