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 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. © 2014 American Chemical Society

Akkaya, E.U.

Turan I.S.

Organic Letters

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 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

Turan, I. S.

Akkaya, E. U.

Bilkent University Institutional Repository

Chemiluminescence Sensing of Fluoride Ions Using a Self-ImmolativeAmplifierIlke Simsek Turan† and Engin U. Akkaya*,†,‡†UNAM-National Nanotechnology Research Center and ‡Department of Chemistry, Bilkent University, Ankara 06800, Turkey*S Supporting InformationABSTRACT: An enhanced chemiluminescence signal is obtainedwhen electronically triggered dioxetane cleavage is initiated byfluoride-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 trappedwithin a PMMA layer on top of a glass plate. In that arrangement,fluoride in aqueous solutions can be detected selectively at lowmicromolar concentrations.Optical sensing of fluoride ions, especially in aqueoussolutions, is very challenging because of their highlyefficient hydration, reducing effective nucleophilicity andbasicity. On the other hand, considering its presence in waterand commercial products and its implication in a number ofhealth problems, monitoring of fluoride concentration is animportant public priority.1 At present, ion-selective electrodesare an option,2 but low-cost and straightforward assessment offluoride ions require other methodologies. There have beenmany proposals for detection of fluoride by using chromogenicand fluorogenic probes,3 some working in organic solvents, andothers operating in aqueous mixtures, all with acknowledgedlimitations 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 peroxidesusually implicated as reactive intermediates in bioluminescenceas well as hydrogen peroxide triggered chemiluminescence ofoxalate derivatives. 1,2-Dioxatenes can be stabilized by theincorporation of bulky groups, including adamantyl or fenchylsubstitutions.4 3-Hydroxyphenyl substituent was shown5 tofunction as an electronic trigger; on deprotonation (phenoxideformation) 1,2-dioxetane ring is cleaved, generating theelectronically excited ester product and eventually relaxingradiatively with a peak emission at 466 nm. The process isknown 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 inall cases, a single fluoride ion triggers decomposition of a singlesubstituted dioxetane.Self-immolation, on the other hand, refers to a veryinteresting chemical conversion typically resulting in completefragmentation of large (even polymeric) molecules.7 Recently,Shabat and co-workers introduced a series of self-immolativelinkers,3j,8 which when used judiciously, lead to valuable signalamplification in chemosensors targeting reactive analytes.In this work, we wanted to incorporate a self-immolativelinker to trigger two chemiluminescence processes at the sametime, in response to single fluoride mediated deprotectionevent. The target molecule was synthesized (Scheme 1) in afew steps from commercially available materials, some in closeanalogy to the literature procedures. To that end, enhanced 3-hydroxybenzaldehyde was reacted with benzoyl chloride, andthe resulting phenyl ester was then converted to adamantyl-3-hydroxyphenyl alkene derivative 4. The self-immolative linkerwas prepared according Shabat and co-workers. Thus,compound 7 was obtained with silyl protection (TBDMS)already in place. Chemiluminogenic units were assembled bythe reaction of activated linker with the 3-hydroxyphenylmoiety of the reporter unit (operation of the fluoride sensor isshown in Scheme 2). In the final step, the electron-rich enolether is efficiently photooxygenated to yield 1,2-dioxetane 9.The 1,2-dioxetane derivative 9 obtained this way is thermallystable and can be stored under ambient conditions. We initiallytested its response to fluoride anions in DMSO. Very brightblue chemiluminescence is triggered on addition of tetrabuty-lammonium fluoride (TBAF). Larger concentrations progres-sively led to more intense luminescence (Figure 1). We alsowanted to demonstrate the selective nature of the chem-iluminescene signal. Treatment with a number of potentialcompetitor anions resulted in very little luminescence or noneat all (Figure 2). The detection limits were calculated(Supporting Information, S11−S14) and determined to be 47μM in DMSO and 0.67 mM in DMSO/aqueous buffer mixture(90/10, pH 7.2).The silyl protection group is stable in DMSO−aqueousbuffer solutions at moderately acidic solutions (e.g., at pH 4.0).Received: February 1, 2014Published: March 7, 2014Letterpubs.acs.org/OrgLett© 2014 American Chemical Society 1680 dx.doi.org/10.1021/ol5003412 | Org. Lett. 2014, 16, 1680−1683Digital photographs of the solutions (Figure 3) show theselectivity of chemiluminescence under ambient light. Fluoridein DMSO or DMSO−buffer mixture elicits a clear responsewith luminescence intensity reflecting fluoride concentration.Chemiluminescence quantum yield was determined (ϕCL =0.46), and to our delight, it is almost twice that of the singlechemiluminescent 1,2-dioxetane unit. Thus, amplificationthrough the use of self-immolative linker was validated.Scheme 1. Synthesis of the Self-ImmolativeChemiluminogenic Fluoride SensorScheme 2. Self-immolation mechanism and multivalentresponseFigure 1. Chemiluminescence spectra of 9 + F− in the presence ofincreasing F− concentrations. Probe concentration is 100 μM inDMSO.Figure 2. Selectivity of chemiluminogenic response. CN− in the formof tetrabutylammonium cyanide elicits very little response. All otheranions tested generated no response in DMSO/PBS buffer (90/10,pH 7.2) Probe 9 concentration is 500 μM.Figure 3. Selective chemiluminescent response of the fluoride probe 9under ambient light.Organic Letters Letterdx.doi.org/10.1021/ol5003412 | Org. Lett. 2014, 16, 1680−16831681We also wanted to demonstrate the response to aqueousfluoride solution in the form of test strips. To that end, weimpregnated PMMA with the chemiluminogen probe 9. Thepolymer strips on glass were prepared. When these probes aredipped into fluoride solutions in THF chemiluminescence istriggered. Again, the luminescence intensity is related to thefluoride concentration in solution (Figure 4). The photographwas digitized, and the brightness of the strips was quantified.The plot of brightness as a function of fluoride concentrationshows a reproducible relation. The effect of water content wasalso investigated by varying the percentage of buffer in DMSO.Because of the thickness of the polymeric layers andinhomogeneity of diffusion of fluoride (Figure 4), the polymerstrips shows bright and dark patches except for the highfluoride case, but the integrated luminescence data (Figure 5)for the chemiluminescence triggered on the strips providesusable analytical data.In conclusion, we demonstrated that multiple chemilumi-nescence events can be triggered through use of a self-immolative linker. This approach offers a chemical avenue forenhancing the signal produced in response to a given analyte.Considering the fact that chemiluminescence in principle canprovide a rapid, qualitative, and/or quantitative test for analytesof interest, we are confident that other probes combining thepower of self-immolation and chemiluminescence will emerge.Rapid assessment of fluoride concentrations in drinking watercould be a possible application, and the bright chemilumi-nescence of the probe 9 or structurally related derivatives couldprovide a promising alternative to current methods.■ ASSOCIATED CONTENT*S Supporting InformationMethods, experimental procedures, and additional spectral data.This material is available free of charge via the Internet athttp://pubs.acs.org.■ AUTHOR INFORMATIONCorresponding Author*E-mail: eua@fen.bilkent.edu.tr.NotesThe authors declare no competing financial interest.■ ACKNOWLEDGMENTSWe gratefully acknowledge support from TUBITAK in theform of a scholarship to IST.■ REFERENCES(1) (a) Farley, J. 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Chemiluminescence sensing of fluoride ions using a self-immolative amplifier

Ilke Simsek Turan

Engin U. Akkaya

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Chemiluminescence Sensing of Fluoride Ions Using a Self-Immolative Amplifier

http://repository.bilkent.edu.tr/bitstream/11693/26300/1/Chemiluminescence%20Sensing%20of%20Fluoride%20Ions%20Using%20a%20Self-Immolative%20Amplifier.pdf

Chemiluminescence sensing of fluoride ions using a self-immolative amplifier

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