This article was published as part of the
Supramolecular chemistry of anionic
species themed issue
Guest editors Philip Gale and Thorfinnur Gunnlaugsson
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3936 Chem. Soc. Rev., 2010, 39, 3936–3953 This journal is
c
The Royal Society of Chemistry 2010
Colorimetric and fluorescent anion sensors: an overview of recent
developments in the use of 1,8-naphthalimide-based chemosensorsw
Rebecca M. Duke,
a
Emma B. Veale,
a
Frederick M. Pfeffer,
b
Paul E. Kruger
c
and
Thorfinnur Gunnlaugsson*
a
Received 20th May 2010
DOI: 10.1039/b910560n
This critical review focuses on the development of anion sensors, being either fluorescent and/or
colorimetric, based on the use of the 1,8-naphthalimide structure; a highly versatile building unit
that absorbs and emits at long wavelengths. The review commences with a short description of
the most commonly used design principles employed in chemosensors, followed by a discussion
on the photophysical properties of the 4-amino-1,8-naphthalimide structure which has been most
commonly employed in both cation and anion sensing to date. This is followed by a review of the
current state of the art in naphthalimide-based anion sensing, where systems using ureas,
thioureas and amides as hydrogen-bonding receptors, as well as charged receptors have been used
for anion sensing in both organic and aqueous solutions, or within various polymeric networks,
such as hydrogels. The review concludes with some current and future perspectives including the
use of the naphthalimides for sensing small biomolecules, such as amino acids, as well as probes
for incorporation and binding to proteins; and for the recognition/sensing of polyanions such as
DNA, and their potential use as novel therapeutic and diagnostic agents (95 references).
Introduction
Anions play a major role in our daily life; being crucial to
physiological function as well as various industrial process.
Consequently, in the environment, anionic species can be
either essential to sustain growth or act as harmful pollutants.
It is therefore not surprising that in the last decade the
development of colorimetric and luminescent sensors for
anions, where the function, concentration and location of
the negatively charged species can be monitored, has become
a very active area of research.
1–4
While earlier examples of anion sensors focused on the
proof of various principles, often using structurally simple
hydrocarbon-based chromophores/fluorophores, furnished
with one or more charged or charge-neutral recognition
moieties, recent anion sensing research has become more
focused.
2,5
Such targeted investigations include the develop-
ment of more specific sensors (e.g. for the recognition of a
particular anion, or family of anions); more potent sensors
(e.g. that can target a particular anion within a given
concentration range); sensors that function in more
competitive media (e.g. aqueous media, for use in
a
School of Chemistry, Centre of Synthesis and Chemical Biology,
University of Dublin, Trinity College Dublin, Dublin 2, Ireland.
E-mail: gunnlaut@tcd.ie, +353 1 896 3459
b
School of Life and Environmental Sciences, Faculty of Science and
Technology, Deakin University, Waurn Ponds, 3217 Australia
c
Department of Chemistry, College of Science, University of
Canterbury, Christchurch, 8020, New Zealand
w Part of a themed issue on the supramolecular chemistry of anionic
species.
Rebecca M. Duke
Rebecca Duke studied
chemistry at Trinity College
Dublin and graduated with
honours in 2005. Under the
supervision of Prof. T.
Gunnlaugsson (Trinity), she
completed her PhD degree in
2009, where she worked on the
development of colorimetric
and fluorescent sensors for
anions. After spending some
time in pharmaceutical
industry, she is currently
carrying out postdoctoral
research with Prof. Pauline
Rudd at the National Institute
for Bioprocessing Research and Training (NIBRT) University
College Dublin.
Emma B. Veale
Emma Veale received her BSc
from National University of
Ireland, Maynooth, and a
PhD in supramolecular and
medicinal chemistry from
School of Chemistry, Trinity
College Dublin. She has been
a senior research fellow in the
group of Prof. Gunnlaugsson
since 2007; working in the
medicinal chemistry areas of
anion recognition and sensing
and supramolecular self-
assembly formations.
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c
The Royal Society of Chemistry 2010 Chem. Soc. Rev., 2010, 39, 3936–3953 3937
environmental, biological or medical applications); and more
economical sensors (e.g. that can be formed in few synthetic
steps using inexpensive starting materials).
6–13
For practical applications, these sensors also need to satisfy
strict photophysical criteria, such as being able to absorb and
emit at long wavelengths to facilitate the use of naked eye
detection or the use of inexpensive optics, posses relatively
long lived excited states,
12
and have high quantum yields.
Due to its unique photophysical properties, the naphthal-
imide structure has found application in many areas of
chemistry.
14,15
Its absorption and fluorescence emission
spectra lie within the UV and visible regions, and the various
photophysical properties can be easily fine tuned through
judicious structural design. Synthetic modifications are readily
accommodated on either the aromatic ‘naphthalene’ moiety
itself, or at the ‘N-imide site’, allowing for varieties of
functional groups and structural motifs to be incorporated.
Consequently, the 1,8-naphthalimide structure has been
extensively used within the dye industry, as strongly absorbing
and colourful dyes, in the construction of novel therapeutics,
16
as well as in the formation of chemical probes,
17–20
particularly
for the sensing of biologically relevant cations.
21–23
It is thus no
surprise that this structure has found application in the field of
anion recognition and sensing, and in the last seven years or so
many excellent examples of naphthalimide-based anion sensors
have been published, clearly demonstrating the versatility of
this structure within this fast growing field of research.
This review will focus on this recent development; beginning
with a short introduction on the design of colorimetric and
fluorescence sensors, followed by a discussion on the photo-
physical properties of naphthalimides which can be easily
tuned through synthetic design. This discussion is followed
by a summary of the use of the naphthalimide structure for
sensing of structurally simple anions and biologically relevant
polyanions such as DNA. The examples presented herein are
mainly grouped by the location of the anion receptor moiety
on the naphthalimide fluorophore (commonly the 4-position
or the 1,8-imide position) and by the structural similarities of
the various anion receptor moieties employed. Finally,
alternative anion sensing mechanisms and the potential use
in other related areas of research involving the naphthalimide
fluorophore will be discussed.
General design principles employed in colorimetric
and fluorescence sensing
There are two main strategies used in the design of colori-
metric and fluorescent sensors for the detection of analytes in
Frederick M. Pfeffer
Fred Pfeffer completed his
PhD in 2001 working with
Professor Richard Russell on
the synthesis of peptide
functionalised molecular frame-
works then moved to Trinity
College Dublin to take up a
temporary lectureship. This
teaching post was followed by
a postdoctoral fellowship with
Thorfinnur Gunnlaugsson and
Paul Kruger on the develop-
ment of naphthalimide based
anion sensors. He returned to
Australia in 2004 to take up a
lecturing position at Deakin
University in the Faculty of Science and Technology where he
is now senior lecturer. His current interests include the develop-
ment of new antidiabetic and antimicrobial agents as well as
supramolecular anion recognition; in particular the development
of conformationally preorganised norbornane based hosts.
Paul E. Kruger
Paul E. Kruger completed his
BSc (Hons) and PhD degrees
in Chemistry at Monash
University under the direction
of Prof. Keith S. Murray, and
then undertook postdoctoral
research with Prof. Vickie
McKee at the Queen’s
University of Belfast. He was
then appointed as a Lecturer
in Inorganic Chemistry at the
University of Dublin, Trinity
College in 1996, before
moving to the University of
Canterbury in 2007 where he
is a Professor of Supra-
molecular and Inorganic Chemistry. His research interests touch
upon all aspects of supramolecular chemistry ranging from
coordination chemistry and metallo-helicate spin-crossover
complexes, through materials and structural chemistry, to
host–guest and anion sensor chemistry.
Thorfinnur Gunnlaugsson
Thorfinnur (Thorri) Gunn-
laugsson currently holds a
Personal Chair in Chemistry,
in the School of Chemistry,
Trinity College Dublin. He
obtained his BSc from Univer-
sity of Iceland; a PhD from
Queen’s University Belfast
and undertook a postdoctoral
fellowship in Durham Univer-
sity before being appointed to
a Lectureship in Medicinal
Chemistry in Trinity College
Dublin in 1998. He became
a Lecturer in Organic
Chemistry in 2000, being
promoted to an Associate Professor in 2004 and a Personal
Chair in 2008. He was an Erskine Fellow in the Department of
Chemistry, University of Canterbury, New Zealand in 2009 and
a Visiting Professor at NEO - Nanostructures Organiques,
Institut des Sciences Mole
´
culaires CNRS/Universite
´
Bordeaux 1,
2008 and in Deakin University, Victoria, Australia in 2005. He
was awarded the Bob Hay Lectureship by the RSC Macrocyclic
and Supramolecular Chemistry Group, in 2006.
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The Royal Society of Chemistry 2010
solution.
24–26
The binding site may be directly attached, or
integrated, into the signalling moiety, such as shown in Fig. 1a.
In such an instance the mechanism for signal transduction
involves interaction of the analyte with a receptor that is part
of the p-system of the signalling moiety. Chromophores which
are directly attached to the receptor mainly consist of organic
dyes such as azobenzene, nitrobenzene, indoaniline, anthra-
quinone, etc.
27
Many chromophores can also be fluorescent
and can therefore give rise to dual responses in both their
absorption and fluorescence emission spectra upon analyte
interaction.
28
Alternatively, the receptor moiety and signalling subunit
may be covalently linked by a ‘spacer’ group, as demon-
strated in Fig. 1b.
29
When covalently linked, the binding event
in colorimetric sensors is in many instances communicated
from the receptor to the chromophore via conjugation with
aromatic compounds such as quinoxaline, oxadiazole
and porphyrin, to name just a few, and this design has
been extensively employed in supramolecular analytical
chemistry.
30
However, covalently linked fluorescent probes mainly
consist of a receptor and fluorophore, which are electronically
independent. The covalent linkage which separates the
receptor and the fluorophore units is typically a short aliphatic
spacer that minimises any ground-state interactions.
31
Photo-
induced electron transfer (PET) sensors are examples of such
‘fluorophore–spacer–receptor’ designs and ‘ideally’ only
changes in their quantum yield or fluorescence intensity occur
upon recognition of the analyte.
32
This design principle,
originally detailed by de Silva et al.
33
and Czarnik et al.
34
has been widely used in chemo-sensing to date.
An alternative is the use of indicator displacement assays
(IDAs) in which a receptor–chromophore or receptor–
fluorophore ensemble is selectively dissociated by the
addition of an appropriate competitive analyte.
30,35,36
The
analyte interacts efficiently with the receptor resulting in a
detectable response of the chromophore or fluorophore.
Such systems have been, in particular, developed by Anslyn
and co-workers as well as Fabbrizzi and co-workers.
37,38
Also, prevalent in the design of chemosensors (particularly
for practical purposes), is the need for reversibility in order to
provide continuous monitoring of the analyte. However, in the
case of ‘once-off’ measurements, such reversibility is not
necessary.
The basic photophysical properties of the
1,8-naphthalimide structure and their earlier
use in fluorescent cation sensing
The photophysical properties of the naphthalimide structure
are governed by the nature of the substituent and the
substitution pattern employed. For instance, 3- or 4-nitro-
1,8-naphthalimides such as 1a, shown in Fig. 2, possess high
energy excited states, as the nitro functional group and the
imide moiety are electron withdrawing. Hence, general
structures such as 1a possess a broad absorption band, with
l
max
centred at about 360 nm, and emit at short wavelengths.
In contrast, reduction of this moiety to give the 4-amino-1,8-
naphthalimide derivative 1b, would give a ‘push–pull’ based,
internal charge transfer (ICT) excited state, caused by the
electron donating amine and the electron withdrawing imide.
This ICT character, which gives rise to a large excited-state
dipole and, in turn, broad absorption and emission bands
centred at ca. 450 and 550 nm, respectively, when recorded in
water (Fig. 1 for 1b). The ICT transition is highly solvent
dependent,
39
as demonstrated in Fig. 3, where both the l
max
of
the absorption and the emission are affected; where polar
protic solvents stabilise the ICT character more than apolar
solvents, e.g. Fig. 3a. This same effect can also be clearly seen
in the fluorescence excitation spectra, Fig. 3b, which also
demonstrates that the fluorescence quantum yield (F
F
) is also
highly solvent dependent.
The 4-amino-1,8-naphthalimide derivatives are usually
found to be highly emissive in organic solvents such as
dichloromethane and chloroform, with F
F
often being
Fig. 1 Schematic representation of design concepts for the construction of colorimetric and fluorescent sensors: (A) The binding side
and the signalling unit are covalently connected with p–p bonds, and anion recognition should give rise to changes in the absorption
spectra and possibly, depending on the nature of the chromophore employed also in the emission spectra. (B) The two parts are
separated by a covalent spacer that does not allow for any ground-state p–p*orn–p* interactions to occur. Hence, such systems
usually give rise to significant changes in the emission spectra upon anion recognition with only minor or no changes in the absorption
spectrum.
Fig. 2 4-Nitro, 1a, and 4-amino-1,8-naphthalimide 1b, structures,
and schematic representation of the ICT excited state within the
4-amino-1,8-naphthalimide fluorophore caused by a ‘push–pull’
action.
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reported to be close to unity; while in water, significant
quenching is observed, i.e. Fig. 3b. Nevertheless, the use of
4-aminonaphthalimide for sensing in water is well established,
particularly for the sensing of cations. Sensors 2–7 are just a
few recent examples where the receptors are connected to the
fluorophore via the amino functionality of the aryl ring. In
these, depending on the design principles employed, the
naphthalimide emission spectra alone (as is usually the case
for PET-based sensors) or the absorption and the emission
spectra were highly modulated upon binding of cations at the
respective binding sites (receptors). Of these, 2 was developed
for the sensing of H
+
, where through an electron-transfer
mechanism, the excited state of the naphthalimide is quenched
upon protonation of the tertiary aliphatic amine.
40
Many
other examples of such pH dependent PET naphthalimide
sensors have been developed to date, for use in solution or
within, or on, solid supports.
18
In contrast, compound 3, possessing a crown ether receptor
was developed for analysis of Na
+
in blood samples,
41
while
4
42
and 5
43
have been developed for detecting Zn(II). Structure
4 has also recently been used for imaging of bone structures
using epifluorescence microscopy.
44
The Zn(II) sensors 4a and
4b, are based on the fluorophore–spacer–receptor principle,
and were shown to bind the Zn(
II) ion in a highly selective
manner at the iminodiacetate moiety, in competitive media at
pH 7.4; this increases the oxidation potential of the receptor,
preventing photoinduced electron transfer quenching taking
place from the receptor to the excited state of the fluorophore,
and hence, this caused the naphthalimide fluorescence to be
‘switched on’. Whether the emission is switched ‘off’or‘on’ for
such PET sensors depends on the changes that occur in the
oxidation or the reduction potential of the receptor, in
comparison to that of the fluorophore, upon analyte
recognition. Here, the 4-amino moiety does not participate
directly in ion binding and hence, the absorption spectrum was
not significantly affected. Similarly, large enhancements were
seen in the emission spectra of 5, developed by Watkinson
et al.,
43
upon binding to Zn(II). Recently, Watkinson et al.,
have extended their design to form naphthalimide dimers,
using Cu(
II) catalysed click chemistry.
45
In contrast, compound 6, developed as sensors for Cu(II),
then upon binding of Cu(
II) does engage the two aryl amines in
the binding.
46
Hence, the absorption spectrum is significantly
affected, and indeed so much so that the binding is visible to
the naked eye; hence 6 is a colorimetric as well as a fluorescent
sensor for Cu(
II). Similarly, 7 showed large changes in the
absorption and the emission spectra of the naphthalimide
moiety upon sensing of Cu(
II),
47
while the mono-
naphthalimide analogue has recently been shown to be a
sensor for Zn(
II).
48
These examples are all based on the use of 4-amino-1,8-
naphthalimide structures, where the focus has been on the
detection of cations, but the 3-amino-1,8-naphthalimide
structures have also been employed in such sensing, as
demonstrated elegantly by de Silva et al.
49
4-Amino-1,8-naphthalimide-based urea and thiourea
sensors for anions
The selection of examples discussed above, clearly demon-
strate the potential of such a structure in sensing technology.
In a similar manner, anion interaction either with or in the
vicinity of such amino–naphthalimide moieties, e.g. at a
receptor site, can also result in modulation of the ICT
Fig. 3 (a) The absorption spectra of 1b when recorded in dichloro-
methane and methanol, demonstrating the effect of the solvent on the
ICT band. (b) The fluorescence emission spectra of 1b in dichloro-
methane, methanol and in water.
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![Fig. 7 The chromogenic response of DMSO solutions of sensor 24c [1 10 3 M] upon interaction with various anions: (a) sensor 24c; (b) 24c + 1 eq. AcO . (c) 24c + 1 eq. H2PO4 (d) 24c + 1 eq. F (e) 24c + F (excess). Ref. 66 – Reproduced by permission of the CNRS and the Royal Society of Chemistry.](/figures/fig-7-the-chromogenic-response-of-dmso-solutions-of-sensor-2w3rmlyg.webp)
