Chemiluminescence sensing of fluoride ions using a self-immolative amplifier

Article abstract of DOI:10.1021/ol5003412

An enhanced chemiluminescence signal is obtained when electronically triggered dioxetane cleavage is initiated by fluoride-mediated deprotection of the silyl-protecting group, followed by self-immolation via 1,4-quinone-methide rearrangement. The reaction

Full text of DOI:10.1021/ol5003412

Letter
pubs.acs.org/OrgLett
Chemiluminescence Sensing of Fluoride Ions Using a Self-Immolative
Amplifier
Ilke Simsek Turan† and Engin U. Akkaya*,†,‡
‡
†UNAM-National Nanotechnology Research Center and Department of Chemistry, Bilkent University, Ankara 06800, Turkey
S
* Supporting Information
ABSTRACT: An enhanced chemiluminescence signal is obtained
when electronically triggered dioxetane cleavage is initiated by
fluoride-mediated deprotection of the silyl-protecting group,
followed by self-immolation via 1,4-quinone−methide rearrange-
ment. The reaction takes place even when the probe is trapped
within a PMMA layer on top of a glass plate. In that arrangement,
fluoride in aqueous solutions can be detected selectively at low
micromolar concentrations.
ptical sensing of fluoride ions, especially in aqueous
solutions, is very challenging because of their highly
In this work, we wanted to incorporate a self-immolative
linker to trigger two chemiluminescence processes at the same
time, in response to single fluoride mediated deprotection
event. The target molecule was synthesized (Scheme 1) in a
few steps from commercially available materials, some in close
analogy to the literature procedures. To that end, enhanced 3-
hydroxybenzaldehyde was reacted with benzoyl chloride, and
the resulting phenyl ester was then converted to adamantyl-3-
hydroxyphenyl alkene derivative 4. The self-immolative linker
was prepared according Shabat and co-workers. Thus,
compound 7 was obtained with silyl protection (TBDMS)
already in place. Chemiluminogenic units were assembled by
the reaction of activated linker with the 3-hydroxyphenyl
moiety of the reporter unit (operation of the fluoride sensor is
shown in Scheme 2). In the final step, the electron-rich enol
ether is efficiently photooxygenated to yield 1,2-dioxetane 9.
The 1,2-dioxetane derivative 9 obtained this way is thermally
stable and can be stored under ambient conditions. We initially
tested its response to fluoride anions in DMSO. Very bright
blue chemiluminescence is triggered on addition of tetrabuty-
lammonium fluoride (TBAF). Larger concentrations progres-
sively led to more intense luminescence (Figure 1). We also
wanted to demonstrate the selective nature of the chem-
iluminescene signal. Treatment with a number of potential
competitor anions resulted in very little luminescence or none
at all (Figure 2). The detection limits were calculated
(Supporting Information, S11−S14) and determined to be 47
μM in DMSO and 0.67 mM in DMSO/aqueous buffer mixture
(90/10, pH 7.2).
O
efficient hydration, reducing effective nucleophilicity and
basicity. On the other hand, considering its presence in water
and commercial products and its implication in a number of
health problems, monitoring of fluoride concentration is an
important public priority.1 At present, ion-selective electrodes
are an option,2 but low-cost and straightforward assessment of
fluoride ions require other methodologies. There have been
many proposals for detection of fluoride by using chromogenic
and fluorogenic probes,3 some working in organic solvents, and
others operating in aqueous mixtures, all with acknowledged
limitations such as low affinity, inhibition of response by water,
limited spectral changes, or lack of selectivity.
As a chemiluminogenic unit, our choice was a stable 1,2-
dioxetane. 1,2-Dioxetanes are four-membered cyclic peroxides
usually implicated as reactive intermediates in bioluminescence
as well as hydrogen peroxide triggered chemiluminescence of
oxalate derivatives. 1,2-Dioxatenes can be stabilized by the
incorporation of bulky groups, including adamantyl or fenchyl
substitutions.4 3-Hydroxyphenyl substituent was shown5 to
function as an electronic trigger; on deprotonation (phenoxide
formation) 1,2-dioxetane ring is cleaved, generating the
electronically excited ester product and eventually relaxing
radiatively with a peak emission at 466 nm. The process is
known as chemically initiated electron exchange luminescence
(CIEEL). There have been previous examples of chemilumino-
genic agents that rely on silyl deprotection by fluoride,6 but in
all cases, a single fluoride ion triggers decomposition of a single
substituted dioxetane.
Self-immolation, on the other hand, refers to a very
interesting chemical conversion typically resulting in complete
fragmentation of large (even polymeric) molecules.7 Recently,
Shabat and co-workers introduced a series of self-immolative
linkers,3j,8 which when used judiciously, lead to valuable signal
amplification in chemosensors targeting reactive analytes.
The silyl protection group is stable in DMSO−aqueous
buffer solutions at moderately acidic solutions (e.g., at pH 4.0).
Received: February 1, 2014
Published: March 7, 2014
© 2014 American Chemical Society
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Letter
Scheme 1. Synthesis of the Self-Immolative
Chemiluminogenic Fluoride Sensor
Figure 1. Chemiluminescence spectra of 9 + F− in the presence of
increasing F− concentrations. Probe concentration is 100 μM in
DMSO.
Figure 2. Selectivity of chemiluminogenic response. CN− in the form
of tetrabutylammonium cyanide elicits very little response. All other
anions tested generated no response in DMSO/PBS buffer (90/10,
pH 7.2) Probe 9 concentration is 500 μM.
Scheme 2. Self-immolation mechanism and multivalent
response
Digital photographs of the solutions (Figure 3) show the
selectivity of chemiluminescence under ambient light. Fluoride
Figure 3. Selective chemiluminescent response of the fluoride probe 9
under ambient light.
in DMSO or DMSO−buffer mixture elicits a clear response
with luminescence intensity reflecting fluoride concentration.
Chemiluminescence quantum yield was determined (ϕCL
=
0.46), and to our delight, it is almost twice that of the single
chemiluminescent 1,2-dioxetane unit. Thus, amplification
through the use of self-immolative linker was validated.
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Organic Letters
Letter
We also wanted to demonstrate the response to aqueous
fluoride solution in the form of test strips. To that end, we
impregnated PMMA with the chemiluminogen probe 9. The
polymer strips on glass were prepared. When these probes are
dipped into fluoride solutions in THF chemiluminescence is
triggered. Again, the luminescence intensity is related to the
fluoride concentration in solution (Figure 4). The photograph
ASSOCIATED CONTENT
* Supporting Information
Methods, experimental procedures, and additional spectral data.
This material is available free of charge via the Internet at
http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: eua@fen.bilkent.edu.tr.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge support from TUBITAK in the
form of a scholarship to IST.
REFERENCES
■
Figure 4. PMMA on glass impregnated with probe 9, exposed to
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