Colorimetric and fluorometric chemosensors for selective signaling toward Ca2+ and Mg2+ by aza-crown ether acridinedione- functionalized gold nanoparticles

Article abstract of DOI:10.1016/j.tetlet.2010.06.041

The aza-crown ether acridinedione-functionalized gold nanoparticles (ACEADD-GNPs) 6 have been synthesized and investigated as a fluorescent chemosensor for metal ions. A blue shift along with an intensity enhancement of emission and color change are obser

Full text of DOI:10.1016/j.tetlet.2010.06.041

Tetrahedron Letters 51 (2010) 4331–4335
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Colorimetric and fluorometric chemosensors for selective signaling toward
Ca2+ and Mg2+ by aza-crown ether acridinedione-functionalized gold
nanoparticles
*
Ranganathan Velu, Vayalakkavoor T. Ramakrishnan, Perumal Ramamurthy
National Centre for Ultrafast Processes, University of Madras, Taramani Campus, Chennai 600 113, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The aza-crown ether acridinedione-functionalized gold nanoparticles (ACEADD-GNPs) 6 have been
synthesized and investigated as a fluorescent chemosensor for metal ions. A blue shift along with an
intensity enhancement of emission and color change are observed in the presence of both Ca2+ and
Mg2+ ions. The enhanced fluorescence intensity is attributed to the photoinduced electron transfer
(PET) suppression through space and color change of the suspension from red to blue due to shifted sur-
face plasmon resonance (SPR) with aggregation of nanoparticles by the sandwich complexation.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 19 March 2010
Revised 4 June 2010
Accepted 9 June 2010
Available online 12 June 2010
Keywords:
Photoinduced electron transfer
Surface plasmon resonance
Aza-crown ether acridinedione
Aggregation
Metal ions
Design of functional nanomaterials is of current interest be-
cause of a variety of potential applications ranging from chemistry
to biological sciences. Metal and semiconductor nanoparticles
exhibit interesting size- and shape-dependent properties.1 The
nanosized metal particles are emerging as important type of color-
imetric reporters because their extinction coefficients are several
orders of magnitude larger than those of organic dyes2 and the
transition of the nanoparticles from dispersion to aggregation leads
to a distinct change in color.3–7 The phenomenon is termed surface
plasmon absorption, and the color change upon aggregation is due
to the coupling of the plasmon absorbances as a result of their
proximity to each other.8,9
Significant progress has been made in recent years in the devel-
opment of functional nanomaterials by designing monolayer-pro-
tected metal clusters10–12 and exploiting them as building blocks
for supramolecular structures and sensory applications.13 Based
on the well-known ability of crown ethers to host s-block metals,14
many fluorescent chemosensors designed in recent years for alkali
and alkaline earth ions contain at least one crown ether moiety (or
a related derivative) which behaves as a ‘recognition subunit’ con-
nected to one or more fluorophores.15 In these systems, the output
signal following the crown/cation interaction (sandwich complex)
involves a change in the emission properties of the fluorophore(s)
and is often related to a PET (photoinduced electron transfer)
process.16 Other examples involving different mechanisms, for
example, photoinduced energy transfer17 excimer or exciplex for-
mation,18 conformational change,19 and proton transfer20 have also
been reported. Recent development of K+ sensors has been inspired
by the concept of the sandwich complex in which the conforma-
tion assembles chromophores in proximity and results in intermo-
lecular interactions that significantly enhance the sensitivity in
absorbance or fluorescence.21–25
In this study, we have synthesized aza-crown ether acridinedi-
one-functionalized gold nanoparticles (ACEADD-GNPs) chemosen-
sor, in which through-space PET occured from the N-atom of the
cation receptor (1-aza-15-crown-5) to the fluorophore unit (acrid-
inedione), resulting in the quenching of the fluorescence of the
ACEADD unit. Fluorescence titration with different cation salts in
an acetonitrile solution of ACEADD showed an increase in the fluo-
rescence intensity due to PET suppression, and the color change is
attributed to aggregation of nanoparticles.
The synthetic procedure is shown in Scheme 1. The reaction of
tetraketone 1 and 1,2-phenylenediamine in acetic acid on reflux
afforded nitroacridinedione 2. A mixture of 2 and lipoic acid in
dry dichloromethane with dicyclohexylcarbodiimide (DCC) on re-
flux afforded the acridinedione amidederivative 3. A mixture of 3,
Zn-dust, and CaCl2 in ethanol on reflux afforded the amino bis-
acridinedione derivative 4. A mixture of 4, pentaethylene glycol
ditosylate, and NaH in DMF on reflux afforded aza-crown ether
acridinedione derivative 5. It was recrystallized from a mixture
(9:1) of CHCl3 and methanol to yield a yellow powder of ACE-
ADD. The synthesis of monolayer-protected clusters (MPCs)
adopted the method reported26 by Brust et al. A comparison of
* Corresponding author. Tel.: +91 44 24540962; fax: +91 44 24546709.
E-mail address: prm60@hotmail.com (P. Ramamurthy).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.06.041

4332
R. Velu et al. / Tetrahedron Letters 51 (2010) 4331–4335
Scheme 1. Schematic illustration of synthesis and assembly of ACEADD-GNPs via the reaction of HAuCl4 with ACEADD.
the FT-IR spectra of ACEADD-GNPs resembles that of 5. NaBH4 re-
duces the disulfide moiety of lipoic acid as well as enables the
formation of metallic gold nuclei, which leads to the formation
of S-Au bond to produce 6 (Fig. S1) as reported by Zhao et al.27
(detailed synthesis and characterization data are given in the
Supplementary data).
Figure 1. HR-TEM micrographs of ACEADD-functionalized gold nanoparticles (6) (a, c) before and (b, d) after addition of 0.081 mM Ca2+ and Mg2+ to a ACEADD-GNPs solution.
(a, c) Spherical shape gold nanoparticles attachment with ACEADD. (b, d) Aggregation in response to addition of Ca2+ and Mg2+
.

R. Velu et al. / Tetrahedron Letters 51 (2010) 4331–4335
4333
0.30
0.25
0.20
0.15
0.10
0.05
0.00
0.20
0.15
0.10
0.05
0.00
300
400
500
600
700
300
400
500
600
700
800
Wavelength, nm
Wavelength, nm
Figure 3. The absorption spectra of 6 upon addition of Mg2+ in acetonitrile.
Figure 2. The absorption spectra of 6 upon addition of Ca2+ in acetonitrile.
units will be capping with the nanogold particle having a total sur-
face area of 63.58 nm2.
The HR-TEM sample of 6 was prepared by drop-casting a dilute
suspension on a carbon-coated copper grid and the images are pre-
sented in Figure 1. Three-dimensional approach in TEM images
indicate that ACEADD may be anchoring on the surface of the gold
nanoparticles (GNPs). The size of GNPs was found to be an average
diameter of 4.5 nm. The GNPs are assumed to be spherical; the
number of ACEADD molecules capping with one gold nanoparticle
of size 4.5 nm can be estimated, if the foot print area of the dithiol
molecule is 0.657 nm.2 This shows that ninety seven (97) dithiol
The absorption and emission maxima of acridinedione dyes in
acetonitrile centered around 380 and 430 nm, respectively. The
absorption at 380 nm is attributed to the intramolecular charge
transfer from the nitrogen to the carbonyl oxygen in the acridined-
ione moiety and the emission at 430 nm to that of the local excited
(LE) state.28,29 In this study, aza-crown ether acridinedione-GNPs
exhibit the absorption spectrum of ACEADD-GNPs 6 that consists
Scheme 2. The possible mechanism of the phenomenon of binding of the free ACEADD-GNPs with Ca2+ and Mg2+
.

4334
R. Velu et al. / Tetrahedron Letters 51 (2010) 4331–4335
Figure 4. Colorimetric responses of ACEADD-GNPs colloidal solutions appear red. However, upon addition of Ca2+ (9.6 Â 10À5 M) and Mg2+ (9.6 Â 10À5 M) the solution
immediately turns blue. Addition of other metal ions did not effect the color change.
0.6
0.8
Increasing [ Ca2+
]
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0.5
0.4
0.3
0.2
0.1
0.0
Increasing [ Mg 2+
]
No Ca2+
550
No Mg2+
450
400
450
500
600
Wavelength, nm
400
500
550
600
Figure 5. The emission (kex = 360 nm) spectra of 6 upon addition of Ca2+ (0–
9.6 Â 10À5 M) in acetonitrile.
Wavelength, nm
Figure 6. The emission (kex = 360 nm) spectra of 6 upon addition of Mg2+ (0–
9.6 Â 10À5 M) in acetonitrile.
of two bands: (i) the additive absorption spectrum of ACEADD due
to ICT around 360 nm and (ii) a broad band in the visible region
around 529 nm, which is attributed to the surface plasmon reso-
nance (SPR) for the stabilized gold nanoparticles.
Crown ethers are known for the unusual property of forming
stable complexes with alkali metals. The exceptional stability cor-
relates, to some extent, with the close fit of the cation to the crown
cavity where, upon complexation, the oxygen atoms lie in a nearly
planar arrangement about the central cation. Although 15-crown-5
complexes best with Na+ and 18-crown-6 favors K+, a sandwich
complex of 2:1 between 15-crown-5 and K+ is also well
known.30–38
in the presence of Ca2+ and Mg2+. An intensity maximum is reached
at [M2+]/6 = 2.5 Â 10À5 M, and the emission maximum shifts as
much as 40 nm (from 440 to 400 nm), when excited at 360 nm
as shown in (Figs. 5 and 6). The corresponding additive absorption
spectrum of ACEADD is not affected but SPR peak is shifted. The
spectral features of blue shifted and intensity enhanced emission
are retained, albeit to a lesser extent, and requiring a higher ratio
of metal ion concentration. With lower concentration of metal
ion, the emission maximum is at 420 nm. The kmax continues to
shift toward blue upon further addition of Ca2+ or Mg2+ (eg.,
kmax = 400 at [M2+]/6 = 2.5 Â 10À5 M). Apparently, the interactions
between 6 and metal ions are weak and the ACEADD-GNPs emis-
sion indicates a symmetrical sandwich-like structure; the blue
shifted form is generally attributed to partially overlapping crown
ether moiety of ACEADD, which might account for the weak emis-
sion of blue shifted ACEADD-GNPs and poor sensitivity of the ACE-
ADD emission to the ground state structure. Accordingly, the
binding of Ca2+ or Mg2+ in 6 not only brings the crown group to-
gether in the ground state leading to the formation of a sandwich
but also prohibits or minimizes such a relaxation event in the ex-
cited state leading to a blue shifted emission. The enhancement
in fluorescence intensity is attributed to the suppression of the
PET process through space. The complexation was established as
2:1 equilibrium from the Benesi–Hinldebrand plot (Figs. S4 and
S5). Addition of other metal ions such as Na+, K+, Sr2+, and Ba2+
showed only marginal changes to the absorption and emission of
6 (Figs. S6 and S7), when compared to those with both Ca2+ and
Mg2+ ions.
Interestingly, addition of Na+ and K+ ions did not alter the
absorption or emission properties of 6 (Figs. S2 and S3). In contrast,
on the addition of Ca2+ or Mg2+ ions (0–9.6 Â 10À5 M), the acetoni-
trile solution of 6 (2.5 Â 10À5 M) showed a red shift in the absorp-
tion maximum. The significant change in the color visible to the
naked eye demonstrates that the ACEADD-GNPs recognize Ca2+
and Mg2+ and lead to the nano aggregation (Figs. 2 and 3). A highly
specific, for both Ca2+ and Mg2+ ions, binding event is achieved by
the cation-induced sandwich-like structure of the aza-crown ether
acridinedione-GNPs Scheme 2 and the resultant nano-Au aggrega-
tion through colorimetric response that is indicated by broadening
and red shifting of surface plasmon resonance peak as reported by
Patel et al.39 and Lin et al.40 The ACEADD-capped gold nanoparti-
cle’s colloidal solution appears red (Fig. 4). However, upon addition
of Ca2+and Mg2+ the solution immediately turns blue. The signifi-
cant change in color demonstrates that the ACEADD-GNPs recog-
nize Ca2+ and Mg2+. This aggregation was further confirmed by
TEM (Fig. 1b and d).
In summary, we have demonstrated that gold nanoparticles
modified with ACEADD in acetonitrile exhibit excellent selectivity
toward Ca2+ and Mg2+, resulting in the enhanced fluorescence
Surprisingly, a pronounced blue shift along with an intensity
enhancement of the ACEADD-GNPs emission was observed for 6

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