This journal is c The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2013 New J. Chem.

Cite this: DOI: 10.1039/c3nj00233k

Thioether-tethered bisquinoline derivatives asfluorescent probes for mercury(II) and iron(III) ions†

Yuji Mikata,*a Fumie Nakagakib and Kaori Nakanishib

Three ethanedithiol-linked bisquinoline derivatives with a different

number of methoxy substituents on the aromatic ring exhibit a

significant fluorescent response toward mercury(II) and iron(III) ions.

Fluorescence enhancement (OFF–ON), ratiometric and fluorescence

quenching (ON–OFF) responses were achieved with the same

molecular skeleton, by changing the methoxy substitution pattern.

Fluorescent probes that are responsive to biologically importantmetal ions are of significant interest. In recent years, manyexamples of such probe molecules have been explored.1 Metalbinding motifs of such compounds often contain nitrogen/oxygenatoms as crown or oligoethyleneoxy ethers, aliphatic/aromaticamines and carboxylates. Examples of target metal ions includeCa2+, Zn2+, Cu+ and Hg2+.

We have previously reported that bisquinoline derivative,BQDMEN (N,N0-bis(2-quinolylmethyl)-N,N0-dimethylethylene-diamine) (Scheme 1), exhibits zinc-specific fluorescenceenhancement.2 Introduction of methoxy substituents on thequinoline rings of BQDMEN improved the fluorescent responseto Zn2+. A quinoline skeleton is an attractive platform forfluorescent probes due to its intrinsic emission propertiesand inherent metal binding ability, which leads to significantreduction of molecular weight and synthetic difficulty. Thus, anumber of simple quinoline-based fluorescent zinc sensorshave been reported.2,3

In this letter, we describe the mercury(II)- and iron(III)-induced fluorescence response of three BQET (S,S0-bis(2-quinolyl-methyl)-1,2-ethanedithiol)4 derivatives (Scheme 1). The compounds,BQET, 6-MeOBQET and TriMeOBQET, differ in only their methoxy

substitution pattern, but exhibit metal-dependent OFF–ON,ratiometric and ON–OFF responses, respectively. Although manymercury-sensing probes have been reported due to the significantinterest in mercury detection in many fields,5 fluorescent mercuryprobes with more sensitive OFF–ON6 or ratiometric6g,7 propertiesare highly desirable. In addition, the development of ratiometricfluorescent probes utilizing the quinoline platform is, even forwell-studied zinc probes, still challenging.3b,8

BQET,4 6-MeOBQET and TriMeOBQET were synthesizedfrom 1,2-ethanedithiol and the corresponding 2-chloromethyl-quinolines and characterized by 1H/13C NMR and elementalanalysis. X-ray crystallographic analysis of 6-MeOBQET furtherconfirmed the molecular structures in the solid state (Fig. 1).

A 34 mM acetonitrile solution at 25 1C was used for spectralmeasurements of BQET derivatives. Upon addition of Hg2+

ions, the UV-vis absorption of the ligand at 306 and 318 nmincreased (Fig. 2a). A distinct isosbestic point was seen at281 nm during the titration from 0 to 0.5 eq. of Hg2+ ions,however, the spectral change continued without an isosbesticpoint up to 1 eq., indicating that the complexation includes 2 : 1and 1 : 1 stoichiometry for the ligand : metal ratio. The spectralchange saturated with 1 eq. of Hg2+ ions, indicating a 1 : 1complex at the final stage of the titration (Fig. S1a, ESI†).

Fig. 2b shows the fluorescence spectral change of BQET withincreasing amount of mercury ions. Upon excitation at 317 nm,BQET exhibits negligible fluorescence. In the presence of 1 eq.of Hg2+ ions, an 80-fold fluorescence enhancement was observed

Scheme 1

a KYOUSEI Science Center, Nara Women’s University, Nara 630-8506, Japan.

E-mail: mikata@cc.nara-wu.ac.jp; Fax: +81 742 20 3095; Tel: +81 742 20 3095b Department of Chemistry, Faculty of Science, Nara Women’s University,

Nara 630-8506, Japan

† Electronic supplementary information (ESI) available: Experimental details,Table S1 and Fig. S1–S15. CCDC 924739 and 924740. For ESI and crystallographicdata in CIF or other electronic format see DOI: 10.1039/c3nj00233k

Received (in Montpellier, France)1st March 2013,Accepted 3rd April 2013

DOI: 10.1039/c3nj00233k

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at 411 nm. The fluorescence increase saturated with 1 eq. ofHg2+ ions, supporting the formation of a fluorescent 1 : 1BQET–Hg2+ complex (Fig. S1b, ESI†). Fig. 3 shows the metalion specificity of the fluorescent response of BQET. The fluores-cence enhancement was specific for Hg2+, in the presence ofFe3+, Pb2+, Cd2+, Cr3+ and Fe2+ with 50, 46, 30, 29% and 17% ofthe Hg2+ intensity, respectively. Other metal ions listed in Fig. 3induce negligible fluorescence enhancement.

X-ray crystallographic analysis of the BQET–Hg2+ complexwas carried out. The asymmetric unit has two crystallographicallyindependent cations, only one of which is shown in Fig. 4. Inaddition to the coordination by the two sulfur and two nitrogenatoms of BQET, the Hg2+ center was supported by a weak

interaction with an oxygen atom of a perchlorate ion. Thisstructure is similar to the previously reported BQET–Cu+

complex.4 In the present BQET–Hg2+ complex, no significantsteric distortion was observed and the bond distances areslightly shortened in comparison to values previously reportedfor quinoline- and thioether-bound mercury(II) complexes withhigher coordination numbers.9

For 6-MeOBQET, the fluorescent response toward Hg2+ ionsis quite different in comparison to BQET (Fig. 5b). Uponexcitation at 334 nm, the ligand fluorescence at 363 nmdecreased and instead, the fluorescence at 443 nm increasedwith added Hg2+ ions. Thus, a clear ratiometric response (Dlem =80 nm; I/I0 (at 363 nm) = 0.028 and I/I0 (at 443 nm) = 10.7 with (I)and without (I0) 1 eq. of Hg2+) was observed (Fig. S2b, ESI†). Inthe UV-vis titration, the absorption at ca. 320–335 nm decreasedand isosbestic points were observed at 278, 317 and 336 nmduring the addition of 0–0.5 eq. of Hg2+ (Fig. 5a). Both spectralchanges stopped at 1 eq. of Hg2+ ions, indicating the formationof a 1 : 1 complex (Fig. S2, ESI†). The metal selectivity of theratiometric response (I443/I363) is shown in Fig. 6, and reveals avery high specificity of 6-MeOBQET toward Hg2+ and Fe3+ ions.The Fe3+ and Hg2+ ions induced similar spectroscopic changes(Fig. S3, ESI†). The Cd2+ ions exhibited a different fluorescencespectrum in comparison to the other metal ions studied (Fig. S4,ESI†), however, the I443/I363 value was in the normal range asshown in Fig. 6. Interestingly, Zn2+ induced no fluorescencespectral change in solution with 6-MeOBQET.

Interestingly, a fluorescence quenching response with Hg2+

ions was observed for TriMeOBQET at 418 nm upon excitationat 334 nm (Fig. 7b and Fig. S5b, ESI†). This fluorescencequenching is similar to that observed for 6-MeOBQET at

Fig. 1 ORTEP plot of 6-MeOBQET at the 50% probability level. Hydrogen atomsare omitted for clarity.

Fig. 2 (a) UV-vis absorption and (b) fluorescence (lex = 317 nm) spectra of34 mM BQET in acetonitrile at 25 1C in the presence of various concentrations ofHg2+ ranging from 0 to 68 mM.

Fig. 3 The relative fluorescence intensity of BQET at 411 nm in the presence of1 equivalent of metal ions in acetonitrile at 25 1C. I0 is the emission intensity ofthe free ligand.

Fig. 4 ORTEP plot of the cationic portion of [Hg(BQET)(ClO4)]ClO4 at the 50%probability level. Hydrogen atoms are omitted for clarity.

Fig. 5 (a) UV-vis absorption and (b) fluorescence (lex = 334 nm) spectra of34 mM 6-MeOBQET in acetonitrile at 25 1C in the presence of various concentra-tions of Hg2+ ranging from 0 to 68 mM.

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363 nm. The metal selectivity of the triMeOBQET fluorescencequenching is shown in Fig. 8 and is similar to that of 6-MeOB-QET at 363 nm (Fig. S6, ESI†). Isosbestic points were observedat 282 and 324 nm in the UV-vis titration of TriMeOBQET withHg2+ ions up to 1 eq. (Fig. 7a and Fig. S5a, ESI†). Again, themetal selectivity of the fluorescence quenching of TriMeOBQETis specific for Hg2+ and Fe3+ ions, but other metal ions alsorespond to this molecule (Fig. 8).

We now have three derivatives that exhibit different fluores-cence responses with the same molecular platform, S,S0-bis(2-quinolylmethyl)-1,2-ethanedithiol (BQET). Fig. 9 and Table 1summarize the fluorescent responses to Hg2+ for the threederivatives. In general, the methoxy substituent enhances thefluorescence intensity of the free ligand, accompanied by along-wavelength shift of the fluorescence maximum wavelength(lem). Similarly, the lem values of the mercury complexes withthese ligands also shifted toward lower energy as the number ofmethoxy substituents increased; however, the fluorescenceintensity of the mercury complex was significantly decreasedwith the trimethoxy-substituted derivative. In the same context,the 6-MeOBQET–Hg2+ complex exhibits comparable fluores-cence intensity with the BQET–Hg2+ derivative in spite of thelarge difference in the fluorescence intensities of the corres-ponding free ligands. This effect of methoxy substitution on thefluorescence intensity of the mercury complexes can be rationalizedby the energy level-dependent spin-orbit coupling effect.6a Theenergy level of the singlet excited state of the quinoline p-systemin the mercury complexes becomes higher as the number ofelectron-donating methoxy groups increases, and as a result theoverlap of this destabilized singlet excited state with a mercuryd-orbital of appropriate energy increases. Such an orbital inter-action induces fluorescence quenching by facilitated intersystemcrossing from the singlet excited state to the triplet excited state ofthe quinoline chromophore, leading to non-radiative decay. In thepresent system, methoxy substitution destabilizes the singletexcited state and promotes metal-induced fluorescence quenching.Thus, relative fluorescence intensity between the free ligand andmercury complex modulates the differential fluorescence responsestoward mercury ions.

In conclusion, three ethanedithiol-linked bisquinoline derivatives(BQETs) with a different number of methoxy substituents exhibit

Fig. 6 The relative fluorescence intensity of 6-MeOBQET at 443 nm and 363 nmin the presence of 1 equivalent of metal ions in acetonitrile at 25 1C.

Fig. 7 (a) UV-vis absorption and (b) fluorescence (lex = 334 nm) spectra of34 mM TriMeOBQET in acetonitrile at 25 1C in the presence of various concentra-tions of Hg2+ ranging from 0 to 68 mM.

Fig. 8 The relative fluorescence intensity of TriMeOBQET at 418 nm in thepresence of 1 equivalent of metal ions in acetonitrile at 25 1C. I0 is the emissionintensity of the free ligand.

Fig. 9 Comparison of fluorescence spectra of 34 mM BQET (circles), 6-MeOBQET(squares) and TriMeOBQET (triangles) in acetonitrile at 25 1C in the absence(open symbols, broken lines) and presence (filled symbols, solid lines) of 1equivalent of Hg2+.

Table 1 Comparison of fluorescence maximum wavelengths (lem) for BQET, 6-MeOBQET, TriMeOBQET and their mercury(II) complexesa

BQET 6-MeOBQET TriMeOBQET

Free ligand — 363 nm (medium) 418 nm (strong)Mercury complex 411 nm (medium) 443 nm (medium) 490 nm (weak)

a Relative fluorescence intensity is indicated in parentheses.

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different fluorescent responses toward Hg2+/Fe3+ ions. Althoughcomplete discrimination between Hg2+ and Fe3+ is not yetachieved, the present research provides useful information forfuture fluorescent probe design strategies that lead to metal ionspecific response. Although application in aqueous media is oneof the possible requisites for mercury probes, considerablefluorescence decrease of the mercury complex was observedfor the present system (Fig. S7, ESI†). Development of BQETderivatives with improved specificity, sensitivity and water-compatibility, as well as elucidation of the detailed mechanismsof the differential fluorescent responses of the BQET derivativesare under investigation in our laboratory.

ExperimentalGeneral

All reagents and solvents used for synthesis were from com-mercial sources and used as received. Acetonitrile (Dojin) wasspectral grade (Spectrosol). 1H NMR (400 MHz) and 13C NMR(100 MHz) spectra were recorded on a JEOL JNM AL-400spectrometer and referenced to internal Si(CH3)4 or solventsignals. UV-vis and fluorescence spectra were measured on aJasco V-660 spectrophotometer and Jasco FP-6300 spectro-fluorometer, respectively. CAUTION: perchlorate salts of metalcomplexes with organic ligands are potentially explosive. All dueprecautions should be taken.

BQET4

To an acetonitrile suspension (30 mL) of 2-chloromethylquino-line hydrochloride (535 mg, 2.50 mmol) and 1,2-ethanedithiol(100 mL, 1.25 mmol) was added potassium carbonate (1.38 g,10.0 mmol) followed by stirring for 2 days under reflux. Afterremoval of the solvent, the residue was extracted with chloroform/water. The organic layer was dried, evaporated, and washedwith acetonitrile to give BQET as a white powder. Yield, 445 mg(1.18 mmol, 94%).

6-MeOBQET

6-MeOBQET was prepared via a similar manner to that forBQET in 61% yield.

TriMeOBQET

TriMeOBQET was prepared via a similar manner to that forBQET in 46% yield.

[Hg(BQET)(ClO4)]ClO4

To an acetonitrile solution of BQET was added an equimolaramount of Hg(ClO4)2�6H2O in ethanol, and the solution waskept at 4 1C under ether diffusion conditions to give colorlesscrystals. Yield, 23%.

X-ray crystallography

Single crystals of 6-MeOBQET and [Hg(BQET)(ClO4)]ClO4 werecovered with Paraton-N oil and mounted on a glass fiber. Alldata were collected at 123 K on a Rigaku Mercury CCD detector,with monochromatic MoKa radiation, operating at 50 kV/40 mA.

Data were processed on a PC using CrystalClear Software(Rigaku). Structures were solved by direct methods (SIR-92)10

and refined by full-matrix least-squares methods on F2

(SHELXL-97).11 Crystal data are summarized in Table S1 (ESI†).CCDC 924739 and 924740 contain the supplementary crystallo-graphic data for this paper.†

Acknowledgements

This work was supported by the Research for PromotingTechnological Seeds, JST, Adaptable and Seamless TechnologyTransfer Program through Target-driven R&D, JST, Grant-in Aidfor Scientific Research from MEXT, Japan and the NaraWomen’s University Intramural Grant for Project Research.

Notes and references

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(i) J. V. Ros-Lis, M. D. Marcos, R. Martinez-Manez, K. Rurackand J. Soto, Angew. Chem., Int. Ed., 2005, 44, 4405.

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