A co-pillar[5]arene sensor for linear biogenic amines

Article abstract of DOI:10.1039/c7cc05157c

A thiolated co-pillar[5]arene was attached to the surface of a gold electrode and shown to give an analyte-selective voltammetric response to linear biogenic amines.

Full text of DOI:10.1039/c7cc05157c

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Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc
first methanofullerene derivatives of Sc
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A co-pillar[5]arene sensor for linear biogenic amines
a
a
a
Raghuram Reddy Kothur , Bhavik Anil Patel and Peter J. Cragg *
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A thiolated co-pillar[5]arene was attached to the surface of a gold pillar[5]arene and the three biogenic amines showed no
3
electrode and shown to give an analyte-selective voltammetric significant differences when assessed by fluorescence. To
response to linear biogenic amines.
exploit the known association between linear polyamines and
pillar[5]arenes, co-pillar[5]arene dithol derivative (Fig. 1) was
1
The linear biogenic amines putrescene, spermine and
spermidine have no intrinsic fluorescent or chromogenic
properties so their detection, and particularly differentiation
between them, is hard to achieve. Although not highly toxic in
themselves, they are indicators of bacterial growth and are
designed to adhere to gold while aligning the macrocyclic
cavity parallel to the metal surfaces so that small molecules
could be detected as they passed through.
40
1
thus markers of food spoilage. Elevated levels of these
biogenic amines, particularly spermidine, are also often found
2
in the urine of cancer patients. Biogenic amine analysis
therefore has applications in food security and clinical
assessment of the efficacy of cancer treatment. They have
been shown to interact favourably with macrocycles known as
pillar[5]arenes which suggests that detection of biogenic
amine complexes could be used to monitor their
3
concentrations. Some progress has been made in this
Fig. 1 Co-pillar[5]arene 1 and monomer 2.
direction with water-soluble pillar[5]arene modified silver
nanoparticles
tetraethylenepentamine
Impedance measurements of
responding
to
spermine,
A gold electrode surface was treated with
whereupon combination of cyclic voltammetry and
impedance was utilised to demonstrate successful binding. Fig
A shows the voltammetric response of 1 mM ferrocyanide on
the gold electrode before and after addition of . The faradaic
responses completely disappear, resulting in a purely
capacitive signal which is suggestive of hindered mass transfer
of ferrocyanide to the electrode surface consistent with the
presence of a surface monolayer.
1 over 4 h
4
and
triethylenetetramine.
surface immobilized
a
a
calix[4]crown-5 can differentiate between levels of spermidine
in urine samples taken from cancerous and non-cancerous
2
1
5
patients and gold nanoparticles coated with a calix[4]crown-5
give a distinctive pink to blue colour change in the presence of
6
either spermine or spermidine. Here we describe a method
which can discriminate between three biogenic diamines.
Since the first report of 1,4-dimethoxypillar[5]arene in
Fig 2B shows the real and imaginary impedance for the
7
2
008 numerous applications have been found for members of
gold electrode before and after treatment with
1. Charge
8
-17
the pillar[n]arene class of macrocycles.
They have been
transfer resistance (R ) significantly increased from 21 ± 0.2 Ω
ct
18-20
employed to detect species as diverse as paraquat,
to 42.3 ± 5.5 Ω following addition of
1 (P < 0.001, n = 3) and
2
1
22
23
dopamine, phosphate and bacterial lectins predominantly
consistent with surface attachment leading to hindered
electron transfer for the redox couple. The ohmic resistance
3,24-39
30-39
by fluorescent
or electrochemical
methods. However,
a pyrene labelled
the association constants between
(
0
RΩ) significantly decreased following attachment of
.001, n = 3) which is also indicative of a surface monolayer
attached to the electrode surface.
1 (p <
a.
School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton,
BN2 4GJ, UK, E-mail: P.J.Cragg@brighton.ac.uk; Fax: +44 (0)1273 642674; Tel +44
(
0)1273 642037.
Electronic Supplementary Information (ESI) available: synthesis of
modification and molecular modelling. See DOI: 10.1039/x0xx00000x
2, electrode
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No faradaic responses were observed for the bare gold
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DOI: 10.1039/C7CC05157C
2 attached, suggesting that oxidation under
electrode or with
the small potential window was not facilitated. The capacitive
current for the electrode with attached was significantly
lower than the gold electrode, suggesting successful
attachment. The electrode modified with showed faradaic
2
1
responses for spermidine with oxidation and reduction peaks
indicating that the electrochemical activity of spermidine is
facilitated through the host-guest interaction with
1.
Fig 2. Evaluation of the attachment of
1 on to a gold surface Consequently it is the presence of the macrocycle on the
through voltammetric (A) and electrochemical impedance surface which facilitates amine binding and detection.
spectroscopy (B) measurements.
Fig 4B shows the voltammetric responses of four different
linear biogenic amines of increasing complexity, putrescine,
spermidine, spermine and n-pentylamine. Fig 4C shows the
response of the oxidation and reduction peak potential (EpA
and EpC, respectively) to the amines which reveals a linear
relationship between the peak potential for oxidation and
reduction decreasing with increasing numbers of amine groups
present. This is consistent with the kinetics for electron
transfer being most favourable for spermine, with four amine
groups and a longer overall chain length, than for n-
pentylamine or putrescine. Fig 4D shows the voltage difference
between EpA and EpA an indicator of kinetic and mass transfer
Fig 3. Amines tested: (from top) pentylamine, putrescine, behaviour of the redox species which is significantly higher for
spermidine and spermine
spermine than putrescine or spermidine (p < 0.05, n = 3). This
suggests that access to the electrode surface is most difficult
To understand how
1
detects the linear biogenic amines for spermine even though it has excellent electron transfer
shown in Fig. 3, voltammetric responses were determined, kinetics. These findings indicate that host-guest interactions
initially with spermidine on the bare gold electrode then the between the co-pillar[5]arene and the linear biogenic amines
electrodes surface-modified with monomer
pillar[5]arene (Fig 4A).
2
or co- facilitate electron transfer from the amine group to the
electrode surface.
1
A linear relationship between the concentration of
spermine and current was observed on the gold electrode
modified with
1 (Fig. S2). The current monitored at EpC was
-1
greater than that for EpA. The sensitivity was 57 nA mM and
the limit of detection was 113 µM. Repeated cycling of the
modified electrodes and daily use over five days resulted in
negligible attenuation of the response to analytes (Fig S3.)
A semiempirical computational investigation of biogenic
amine complexion by 1,4-dimethoxypillar[5]arene, as a model
for
1, suggests that the amines approach the macrocycle
before threading through (see ESI). As this process proceeds
the number of intermolecular hydrogen bonds increases,
leading to increasing ΔG(binding) values and the formation of
pseudorotaxanes analogous to those observed in other
3,27
pillar[5]arene-amine complexes. We propose that reversible
formation of rotaxanes between macrocycle and linear
1
Fig. 4 Detection of linear biogenic amines: (A) response of amines generates the voltammetric signal and reversible peaks
spermidine on a gold electrode with and without attachment occur when the amine is bound by the macrocycle. A similar
of
putrescine (PUT) spermidine (SPD) and spermine (SPR) on a amines by calix[4]crown-5.
gold electrode with attached, (C and D) responses of In conclusion, we have demonstrated that electrochemical
oxidation peak potential (EpA) and reduction peak potential detection of putrescine, spermidine and spermine is facilitated
EpC) for the biogenic amines and difference between the EpA through complexation between the co-pillar[5]arene and the
1 and 2, (B) voltammetric responses of pentylamine (PA), mechanism has been suggested for the complexation of
5
1
(
and EpC (mean ± S.D., n=3, *p < 0.05)
linear biogenic amine. The resultant faradaic response is
dependent on the number of amine groups and carbon chain
length within each biogenic amine. While other macrocyclic
2
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3-6
2
7 P. Wang, Y. Yao and M. Xue, Chem. Commun., 2014, 50
,
systems have been used to detect linear polyamines, this
approach is able to rapidly differentiate between biogenic
amines.
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064.
DOI: 10.1039/C7CC05157C
2
2
8 Y. Sun, J. Wang and Y Yao, Chem. Commun., 2017, 53, 165.
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3
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0 B. Xia and M. Xue, Chem. Commun., 2014, 50, 1021.
1 J. Zhou, M. Chen, J. Xie and G. Diao, ACS Appl. Mater.
Conflict of interest
Interfaces, 2013, 5, 11218.
There are no conflicts to declare.
3
3
2 R. R. Kothur, J. Hall, B. A. Patel, C. L. Leong, M. G. Boutelle
and P. J. Cragg, Chem. Commun., 2014, 50, 852.
3 V. A. Smolko, D. N. Shurpik, R. V. Shamagsumova, A. V.
Porfireva, V. G. Evtugyn, L. S. Yakimova, I. I. Stoikov and G. A.
Evtugyn, Electrochim. Acta, 2014, 147, 726.
Acknowledgements
RRK thanks the University of Brighton for a studentship. PJC
thanks the US Army Research Office for financial support
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