A chromogenic dioxetane chemosensor for hydrogen sulfide and pH dependent off-on chemiluminescence property

(1)

ContentslistsavailableatScienceDirect

Sensors

and

Actuators

B:

Chemical

j ou rn a l h o m ep a g e :w w w . e l s e v i e r . c o m / l o c a t e / s n b

A

chromogenic

dioxetane

chemosensor

for

hydrogen

sulﬁde

and

pH

dependent

off–on

chemiluminescence

property

Ilke

Simsek

Turan,

Fazli

Sozmen

∗

UNAM—NationalNanotechnologyResearchCenter,BilkentUniversity,Ankara06800,Turkey

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received6February2014

Receivedinrevisedform28April2014 Accepted29April2014

Availableonline9May2014 Keywords: Hydrogensulﬁde 1-2Dioxetanes Chemosensors Chemiluminescence

a

b

s

t

r

a

c

t

Inthispaper,arapidandhighlyselectivechromogenicnakedeyedetectionofhydrogensulﬁdewas achievedby a1,2-dioxetane based chemiluminescent probe in aqueousmedia at pH 7.4. Chemi-luminescencepropertyoftheprobecanbemodulateddependingonthepHvalueofmedium.

1. Introduction

The emission of light produced by a chemical reaction is describedaschemiluminescenceandthisphenomenonisutilized in nature frequentlyand referred toas bioluminescence [1–5]. The mostknown bioluminescenceassayis derived fromfirefly luminescencethatarisesfromluciferasecatalyzedaerobic oxida-tionofluciferin[6].Amongthemostpopularchemiluminescent substratessuchasoxalateesters,luminol,acridiniumesters, 1,2-dioxetanes havereceiveda great deal ofattention dueto their unique emission properties [7,8]. Following the synthesis of a firstmemberofdioxetanesbyKopeckyandMumford,many four-memberedring peroxidederivatives havebeensynthesized[9]. Theunimolecular or catalyzeddecomposition of1,2-dioxetanes resultinchemiluminescenceemission.Theunimolecularthermal decompositionof 1,2-dioxetaneshavingunchargedsubstituents canbeexplainedwithconcertedandbiradicalmechanisms.Inthe thermallyinducedconcertedmechanism,twocarbonylproducts which oneof them is inthe singlet ortriplet excitedstateare formeddirectlyviahomolyticcleavageoftheC CandO Obonds offourmemberedring.Inthebiradicalmechanism,an intermedi-atesingletbiradical,whichcanyieldcarbonylproducts,isformed [10,11].Thelatterdecompositionmechanismof1,2-dioxetanesis thechemically initiated intramolecularcharge transfer induced

∗ Correspondingauthor.Tel.:+903122903568/+905554811949. E-mailaddresses:sozmen@unam.bilkent.edu.tr,fsozmen@hotmail.com (F.Sozmen).

chemiluminescence(CTICL)ofdioxetanes.IntheCTICLmechanism, decompositioniscatalyzedbysubstratessuchasabaseorametal ion.Generallythehydroxyphenylgroupisoftenusedasan aro-maticelectrondonor.Thedeprotanationofhydroxyphenylgroup leadstoformationof ananionicphenolate groupwhich causes intramolecularchargetransfer(CT).TheCToccursfromphenolate totheO Oofdioxetanesinordertoinducedecompositioninto respectiveexcitedspecies[11].

Redoxactivesulfurcontainingmoleculeswhichareknownas reactive sulfur species (RSS) play crucial roles via oxidation or reductionofbiomoleculesunderphysiologicalconditions[12–17]. Onememberofthisfamily ishydrogensulﬁde (H2S)whichhas

acharacteristicfoulodorofrottenegg.Sinceendogenously pro-ducedH2Shassigniﬁcantrolesinbiologicalsignalingandmetabolic

processsuchasmodulationofneurotransmission,cardiovascular protection,regulationofcellgrowth,stimulationofangiogenesis, detectionofthismoleculeattractsgrowinginterestinliterature [17–25].

Achromogenicchemosensorgenerallytransducesachemical signalintoacolorchangeandthistypeofsensingattractedmuch attentionlasttwodecades[25–30].Inthisstudy,wedesignedand synthesizedanovelfastresponding1,2-dioxetanebaseda chro-mogenicprobe6forsensingH2S.Afterthedesignofprobe6,itwas

synthesizedinsixsteps.ThedetectionofH2Swasachieved

suc-cessfullybyprobe6andthehighlyselectivesensingprocesscanbe monitoredbyacolorchangeofsolutionwithnakedeyeandalso viaappearanceofanewabsorbancebandinelectronicabsorption spectraatpH7.4.Ontheotherhand,chemiluminescenceofprobe

6obtainedatpH12.4sinceitdecomposedatthispHvalue.

(2)

2. Materialsandmethods

2.1. Materials

4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) waspurchasedfromSigma–Aldrich.Sodiumhydroxide solution (0.1mol/L)wasaddedtoaqueousHEPES(100mmol/L)toadjust thepHto7.4.Spectrophotometric gradesolventswereusedfor spectroscopyexperiments. Flashcolumn chromatography (FCC) wasperformedbyusingglasscolumnswithaﬂashgradesilicagel (MerckSilicaGel60(40–63␮m)).Reactionsweremonitoredby thinlayerchromatography(TLC)usingprecoatedsilicagelplates (MerckSilicaGelPF-254),visualizedbyUV-Vislight.Allorganic extractswere dehydratedover anhydrous Na2SO4 and

concen-tratedbyusingrotaryevaporatorbeforebeingsubjectedtoFCC. Allotherchemicalsandsolventsweresuppliedfromcommercial sourcesandusedasreceived.

2.2. Instruments

A pH meter (Oakton, manufactured by Eutech instruments) wasusedtodeterminethepH.Ultraviolet–visible(UV–vis)spectra were recorded on a Varian Cary 100 UV–vis spectrophotome-ter. Chemiluminescence measurements were doneon a Varian Eclipsespectroﬂuorometer.1_H_NMR_and 13_C _NMR_spectra_were

recorded onBruker Spectrospin Avance DPX 400spectrometer usingCDCl3 as thesolvent.Chemicalshifts values arereported

inppmfromtetramethylsilaneasinternalstandard.Spin multi-plicitiesarereportedasthefollowing:s(singlet),d(doublet),m (multiplet).HRMSdatawereacquiredonanAgilentTechnologies 6530Accurate-MassQ-TOFLC/MS.

2.3. Synthesisofcompounds

2.3.1. Synthesisof3-benzyloxybenzaldehyde(₁₎

3-Hydroxybenzaldehyde(1g,8.19mmol)wasdissolvedindry THF. When reaction mixture was cooled to 0◦C, triethylamine (TEA)(1.71mL,12.2mmol)wasaddedandmixedfor20min.After the addition of catalytic amount of 4-(dimethylamino)pyridine (DMAP),benzoylchloride(1.38mL,12.2mmol)wasadded drop-wise to the reaction mixture and it was left to stir at room temperature.Theprogressofthereactionwasmonitoredbythin layerchromatography(TLC).WhenTLCshowednostarting mate-rial,reactionwasconcentratedtohalfofit.Theresiduewasdiluted withethylacetate (EtOAc)and extractedwithbrine.Combined organicphasesweredriedoveranhydrousNa2SO4.Afterremoval

of thesolvent, theresidue waspuriﬁed by silica gel ﬂash col-umnchromatographyusingEtOAc/Hexane(1:5,v/v)astheeluent. Compound1wasobtainedaswhitesolid (1.41g,76%).1_H_NMR

(400MHz,CDCl3):ıH10.04(s,1H),8.23(d,J=8.4Hz,2H),7.78–7.82

(m,2H),7.57–7.69(m,2H),7.51–7.57(m,3H).13_C_NMR₍₁₀₀_MHz,

CDCl3)ı191.1,164.8,151.5,137.8,133.9,130.24,130.21,129.0,

128.71,128.69,127.9,127.3,122.5ppm.

2.3.2. Synthesisof3-benzyloxybenzaldehydedimethylacetal(2)

Compound1(1g,4.42mmol),2,2-dimethoxypropane(1.2mL) andcatalyticamountofp-toluenesulfonicacidwasmixedat75◦C. Theprogress ofthereaction wasmonitoredbyTLC.WhenTLC showednostartingmaterial,reactionwasconcentratedtohalfof it.TheresiduewasdilutedwithEtOAcandextractedwithbrine. Combined organic phases were dried over anhydrous Na2SO4.

After removal of the solvent, the residue was puriﬁed by sil-icagel ﬂash columnchromatography using EtOAc/Hexane (1:5, v/v) as the eluent. Compound 2 was obtained as white solid (745mg,62%).1_H_NMR₍₄₀₀_MHz,_CDCl 3):ıH8.24(d,J=8.49Hz, 2H),7.65(t,J=7.41Hz,1H),7.39–7.55(m,5H),7.23(d,J=8.0Hz, 1H),5.48(s,1H),3.37(s,6H).13_C_NMR₍₁₀₀_MHz,_CDCl 3)ı165.1, 151.0,140.0,133.6,130.1,129.5,129.3,128.6,124.2,121.7,120.2, 102.2,52.5ppm.MS(TOF-ESI):m/z:CalcdforC16H16O4:295.09408

[M+Na]+_,_Found:_295.09078_[M₊_Na]+_,₌_11.18_ppm.

2.3.3. Synthesisofdimethyl1-methoxy-1-(3-benzyloxyphenyl) methylphosphonate(3)

Trimethylphosphite(0.3mL,2.58mmol)wasaddedtothe solu-tionofcompound2(500mg,1.84mmol)inDCMat−78◦_C_under

argon.15minlater, TiCl4 (0.3mL,2.58mmol) wasadded

drop-wisetothereactionmixtureat−78◦_C._The_mixture_was_stirred

for 30min before allowingit toroom temperature and stirred atroomtemperatureforfurther1h.Aftertheadditionof aque-ousmethanol(2:1),reactionmixturewasdilutedwithDCMand extractedﬁrstwithsaturatedsolutionofNaHCO3thenwithbrine.

CombinedorganicphasesweredriedoveranhydrousNa2SO4.After

removalofthesolvent,theresiduewaspuriﬁedbysilicagelﬂash columnchromatographyusingEtOAcastheeluent.Compound3

wasobtainedas white solid (583mg, 91%).1_H _NMR ₍₄₀₀_MHz,

CDCl3):ıH8.22(d,J=8.27Hz,2H),7.66–7.68(m,1H),7.52–7.55 (m,2H),7.48(t,J=7.86Hz,1H),7.38(d,J=7.74Hz, 1h),7.34(s, 1H), 7.24(d, J=8.01Hz, 1H), 4.60 (d, J=15.8Hz, 1H), 3.74 (dd, J=7, 10, 6H),3.45 (s, 3H).13_C _NMR ₍₁₀₀_MHz, _CDCl 3)ı 165.0, 151.19,151.16,136.1,133.6,130.1,129.6,129.5,128.6,125.4,125.3, 121.97,121.94,121.19,121.14,80.7,79.0,59.0,58.8,53.98,53.92, 53.8,53.7ppm.MS(TOF-ESI):m/z:CalcdforC19H17O6P:373.07657

[M+Na]+_,_Found:_373.07657_[M₊_Na]+_,₌_12.27_ppm.

2.3.4. Synthesisof 1-(2-adamatylidene)-1-methoxy-1-(3-hydroxyphenyl)methane(4)

Lithiumdiisopropylamide(1.8mL,3.07mmol)wasadded drop-wisetothereactionmixtureofcompound3(430mg,1.23mmol) dissolvedin1mLdryTHFat−78◦_C_under_argon._After_stirring_of_the

reactionmixturefor45min,2-adamantanone(166mg,1.11mmol) dissolvedindryTHFwasaddeddropwisetothereactionmixture at−78◦_C _under _Ar. _Reaction_was_left_to _stir_at _room

tempera-tureovernight.Afterpouringitintophosphatebuffer(0.2M,pH 7),it wasextractedwithEtOAc.Combinedorganicphaseswere driedover anhydrousNa2SO4.Afterremovalofthesolvent,the

residuewaspuriﬁed bysilicagelﬂashcolumn chromatography using EtOAc/Hexane (1:5, v/v) as the eluent. Compound4 was obtainedaswhitesolid(312mg,94%).1_H_NMR₍₄₀₀_MHz,_CDCl

3): ıH7.17(s,br,1H),7.09(t,J=7.83Hz,1H),6.81(s,1H),6.70–6.77 (m,2H),3.24(s,3H),3.15(s,1H),2.57(s,1H),1.67–1.85(m,14H). 13_C _NMR ₍₁₀₀_MHz, _CDCl 3) ı 155.8, 142.8,136.7, 132.4, 129.1, 121.8,115.9,114.6,57.7,39.1,39.0,37.1,32.2,30.3,28.2ppm.MS (TOF-ESI):m/z: Calcdfor C18H22O2:271.16926 [M+H]+,Found:

271.16357[M+H]+_,₌_13.59_ppm.

2.3.5. Synthesisof 1-(2-adamatylidene)-1-methoxy-1-(3-(2,4-dinitrophenoxy)phenyl)methane(5)

Compound4(100mg,0.37mmol)wasdissolvedin1mLDMF and K2CO3 (153mg, 1.11mmol) was added and the reaction

mixturewasstirredfor5minatroomtemperature. 2,4-dinitro-1-ﬂuoro-benzene(68.9mg,0,37mmol)wasaddedandthereaction mixture was left to stir at room temperature. The progress of thereactionwasmonitoredbyTLC.WhenTLCshowedno start-ingmaterial,theresidue wasdilutedwithEtOAcand extracted withbrine.Combinedorganicphasesweredriedoveranhydrous Na2SO4. Afterremoval of thesolvent, theresidue was puriﬁed

by silicagel ﬂash column chromatography using EtOAc/hexane (1:5,v/v)astheeluent.Compound5wasobtainedaswhitesolid (143.6mg,89%).1_H_NMR₍₄₀₀_MHz,_CDCl 3):ıH8.88(d,J=2.08Hz, 1H),8.36(dd, J=2.95, 9.23Hz,1H),7.47(t,J=7.75Hz, 1H),7.31 (s,1H),7.07–7.12(m,3H),3.34(s,3H),3.26(s,1H),2.66(s,1H), 1.77–2.01 (m, 14H).13_C _NMR ₍₁₀₀_MHz, _CDCl 3)ı 156.0, 153.5,

(3)

Scheme1. Synthesisofprobe6.

142.1,141.4,139.5,138.64,130.2,128.8,127.4,122.0,119.2,118.6, 58.0, 39.1,38.9, 37.0, 32.3,30.3, 28.1. MS(TOF-ESI): m/z:Calcd forC24H24N2O6:435.15616[M H]−,Found:435.15452[M H]−,

=3.77ppm.

2.3.6. Synthesisof4-methoxy-4-(3-(2,4-dinitrophenoxy) phenyl)spiro[adamantine-2,3-[1,2]-dioxetane(6)

Compound 5 (143.6mg, 0.37mmol) was dissolved in DCM. Methyleneblue(5mg)wasaddedtothereactionmixturewhich was irradiated while oxygen gas was passing through it. The progressofthereactionwasmonitoredbyTLC.WhenTLCshowed nostartingmaterial,themixturewasconcentratedundervacuo andtheresiduewassubjectedtothesilicagelﬂashcolumn chro-matographybyusingDCMastheeluent.Compound6wasobtained aswhitesolid(162.8mg,94%).1_H_NMR₍₄₀₀_MHz,_CDCl 3):ıH8.88 (t,J=2.59Hz,1H),8.36(dt,J=2.65,9.24Hz,1H),7.60(m,b,4H), 7.21–7.24(m,1H),6.99(d,J=9.23Hz,1H),3.27(s,3H),3.05(s,1H), 2.12(s,1H),1.90–1.50(m,14H).13_C_NMR₍₁₀₀_MHz,_CDCl 3)ı155.8, 153.8,141.6,139.6,138.1,130.6,128.8,122.1,121.4,118.1,111.2, 50.0,36.2,34.7,33.2,32.9,32.1,31.6,31.4,25.9ppm.

3. Resultsanddiscussions

3.1. Synthesisofprobe₆

Thesyntheticroutetowardprobe6isdepictedinScheme1. Initially 3-hydroxybenzaldehyde was converted to a benzoyl derivative 1 to prevent any polymerization reaction dur-ing the preparation of dimethyl acetal 2. After that, dimethyl acetal 2 was synthesized by using 2,2-dimethoxypropane and

toluene-4-sulfonicacidasacatalyst.Then||-methoxyphosphonate

3wasobtainedinthepresenceoftrimethylphosphiteandTiCl4

asaLewisacid.Subsequenttreatmentofthephosphonate3tothe Wittig–Hornerreactionwith2-adamantanoneyieldedcompound

4.Thencompound5wassynthesizedbythereactionbetween4

and 1-ﬂuoro-2,4-dinitrobenzeneunderbasicconditionsthrough nucleophilicsubstitution.Finally,1,2dioxetanederivative6was synthesizedwiththe[2+2]cycloadditionofsingletoxygen1_O

2on

enoletherofcompound5(Scheme2).

3.2. ElectronicabsorptionspectraforH2Sdetection

Theﬁrst importantobservationwasthecolorimetric change inthesolutionofprobe6inthepresenceofNa2S(acommonly

employedH2Sdonor)atpH7.4.TheconcentrationratiosofS2-,HS−

andH2SaredeterminedbythepHofthebuffer.Thetimedependent

electronicabsorptionspectrawereexaminedfor100␮Mprobe6

in100mMHEPESbuffer/DMSO(1:9,v/v,pH7.4,25◦C)(Fig.1aand b).Uponadditionof10equiv.ofH2S(inHEPESbuffer,100mM)

at pH7.4a newabsorption bandappearedat 468nm immedi-ately,withinaminute,andreachedequilibriumafterabout30min. Thedecompositionofprobe6withH2SatpH7.4resultedinthe

releaseofdinitrothiophenolgroupwhichisresponsiblefor appear-anceofanewabsorbancebandat468nminelectronicabsorption spectrum.TitrationwithvaryingconcentrationsofH2SinHEPES

buffer(100mM,pH7.4)clearlyshowedaprogressiveincreaseof theabsorptionintensity.Fortitrationexperiment,theelectronic absorptionspectrawerecollected10minaftertheeachadditionof H2S(Fig.1c)andthecolorchangewaseasilydistinguishablewith

nakedeye.

(4)

Fig.1. (a)Timedependenceofelectronicabsorptionspectraof100␮Mprobe6in 100mMHEPESbuffer/DMSO(1:9,v/v,pH7.4,25◦C)with10equiv.H2S.(b)Time

dependenceofelectronicabsorptionspectraofprobe6(100␮M)in100mMHEPES buffer/DMSO(1:9,v/v,pH7.4,25◦_C)_with₁₀_equiv._H₂_S_at₄₆₈_nm._(c)_The_electronic

absorptionspectraofprobe6(100␮M)in100mMHEPESbuffer/DMSO(1:9,v/v,pH 7.4,25◦_C)_in_the_presence_of_0–10_equiv._H₂_S_in_HEPES_buffer₍₁₀₀_mM,_pH_7.4).

3.3. Chemiluminescencemeasurements

OnceH2SsolutioninHEPESbufferat pH7.4 wasaddedthe

solutionofprobe6in100mMHEPESbuffer/DMSO(1:9,v/v,pH 7.4,25◦C),adarkyellowchromogenicchangewasobservedwithin theﬁrst minute due to therelease of dinitrothiophenolgroup.

Fig. 2.(a) Light emission spectra of probe 6 (100␮M) in 100mM HEPES buffer/DMSO(1:9,v/v,pH7.4,25◦_C)_with10_equiv._H₂_S_(in_HEPES_buffer,₁₀₀_mM)

atpH12.4andwithoutH2SatpH12.4.(b)Timedependenceofchemiluminescence

spectraofprobe6(100␮M)in9DMSO-1HEPESbuffer(100mM,pH7.4)with 10equiv.H2SandwithoutH2SatpH12.4.(c)Thedigitalphotographof

chemi-luminescenceofprobe6in100mMHEPESbuffer/DMSO(1:9,v/v,pH7.4,25◦C) with10equiv.H2SatpH12.4.(d)Thedigitalphotographofchemiluminescenceof

probe6in100mMHEPESbuffer/DMSO(1:9,v/v,25◦_C)_at_pH_12.4.

However,luminescencecannotbeobservedsincecompound7was notdeprotonatedatpH7.4(chemiluminescenceoff).Tothatend, thepHofsolutionwasadjustedto12.4byNaOHsolution(10N) andbecauseofdecompositionof8viaintramolecularcharge trans-fer,luminescenceofsolutionwasobserved(chemiluminescence on). On the other hand, when pH of probe 6 (100mM HEPES buffer/DMSO(1:9,v/v,pH7.4,25◦C)wasreachedtopH12.4 with-outaddinganyH2Ssolution,almostsameluminescencevaluewas

measured(Fig.2a–d).Theonlydifferencebetweentwocasesare substanceswhicharereleased.Thus,anon–offchemiluminescence wasachievedbyprobe6dependingonpHofthemedium.

(5)

Fig.3.(a)Theelectronicabsorptionspectraof‘probe6+H2S’and‘probe6+various

relatedspecies’(H2Sandotherspecieswere10equiv.inHEPESbuffer100mM,pH

7.4).Probe6concentrationwas100␮Min100mMHEPESbuffer/DMSO(1:9,v/v, pH7.4,25◦_C)._(b)_Digital_photograph_shows_the_appearance_of_the_solutions_under

ambientlight.Probeconcentrationswere100␮M,H2Sandotherrelatedspecies

wereaddedat10equiv.,allin100mMHEPESbuffer/DMSO(1:9,v/v,pH7.4,25◦_C).

Photographwastaken10minaftertheadditionofallspecies.

3.4. Selectivityoverotherrelatedspecies

Further,weevaluatedtheselectivityofprobe6bytreatingwith otherrelatedspecies,includingvariousreactivesulfurspeciesand representativeanions(Fig.3aandb).Onlyprobe6promoted signiﬁ-cantabsorbancechangeat468nm,conformingthehighselectivity ofprobe6forH2S.Theelectronicabsorptionspectraweretaken

10minaftertheadditionofallspecies.Alsodigitalphotographin Fig.3bshowsthatthecolorchangesof100␮Mprobe6solutions(in 100mMHEPESbuffer/DMSO(1:9,v/v,pH7.4,25◦C))whichwere preparedbyadding10equiv.solutionsofglutathione(GSH), cys-teine(cys),H2O2,KCN,Na2S2O3,KSCN,Na2SO3,KF,NaN3,NaNO2

andH2Sin100mMHEPESbuffer/DMSO(1:9,v/v,pH7.4,25◦C).The

digitalphotographwastaken10minaftertheadditionofsolutions. Thus,asshownindigitalphotograph(Fig.3b),ahighlyselective andveryfastnakedeyecolorimetricdetectionofH2Sispossible.

AlsothespectaculardifferencebetweenH2Sandtheotherrelated

speciesintermsofabsorbanceisclearlyshowninthebargraphs (Fig.3c).

3.5. Proposeddecompositionmechanism

Allexperimentsareincompleteagreementwiththefollowing mechanismsdescribedinScheme1.OnceH2SsolutioninHEPES

buffer at pH 7.4 was added, the thiolysis of the dinitrophenyl etheryieldedmixed7anddinitrothiophenolwhichmainlycaused newabsorptionbandnamelyadarkyellowcolorchange.The HR-ESI mass spectral analysis in thenegative mode clearly shows thereleaseofdinitrothiophenolgroup(Fig.S17).AtpH12.4,the deprotanationofhydroxyphenylgroupof7leadstoananionic phenolategroup.Thenegativelychargedphenolategroupcauses intramolecularchargetransfer(CT)fromphenolatetoO Oof diox-etanestoinducedecompositionintoexcited9whichreturnstothe groundstatethroughlightemissionand releaseadamantanone. Furthermore,whenthepHofprobe6wasadjustedpH12.4,the removalofdinitrophenolategroupwhichwasconﬁrmedby HR-ESImassspectrometry(negativeionmode)(Fig.S19)resultsinthe formationofdeprotonated8whichdecomposedtogivetheexcited compound9thatreturnstothegroundstatethroughlightemission inthesameway.

4. Conclusion

In summary, we synthesized a novel fast responding 1,2-dioxetanederivativeprobe6forsensingofH2S.Forchromogenic

chemosensing processes, a new absorption band appeared at 468nm due to the release of dinitrothiophenol group in the presence of H2S, and highly selective and sensitivenaked eye

chemosensingprocesswasobservedforH2S.AlsowhenpHof

solu-tionwasadjustedto12.4,strongchemiluminescenceofsolution was obtaineddue to theremoval of dinitrothiophenol or dini-trophenolategroups.Thedemonstrationsshowninthisworkare signiﬁcantsincethesynthesisofadioxetanebasedhighlyselective, sensitiveandrapidchromogenicH2Sdetectionandmodulationof

chemiluminescencecharacterbypHwaspresentedfor theﬁrst time.

Acknowledgment

TheauthorsthankProfessorDr.EnginU.Akkayaforfruitful dis-cussions.

AppendixA. Supplementarydata

Supplementarydataassociatedwiththisarticlecanbefound,in theonlineversion,athttp://dx.doi.org/10.1016/j.snb.2014.04.101.

References

[1]M.L.Grayeski,Chemiluminescenceanalysis,Anal.Chem.59(1987)1243–1256. [2]F.McCapra,Anapplicationofthetheoryofelectrocyclicreactionsto

biolumi-nescence,J.Chem.Soc.,Chem.Commun.3(1968)155–156.

[3]W.Adam,G.Cilento,ChemicalandBiologicalGenerationofExcitedStates, AcademicPress,NewYork,NY,1982.

[4]E.Sagi,N.Hever,R.Rosen,A.J.Bartolome,J.R.Premkumar,R.Ulber,O.Lev, T.Scheper,S.Belkin,Fluorescenceandbioluminescencereporterfunctions ingeneticallymodiﬁedbacterialsensorstrains,Sens.Actuators,B:Chem.90 (2003)2–8.

[5]R.D.Chaudhari,A.B.Joshi,R.Srivastava,Uricacidbiosensorbasedon chemi-luminescencedetectionusinganano-microhybridmatrix,Sens.Actuators,B: Chem.173(2012)882–889.

[6]E.H.White,E.Rapaport,T.A.Hopkins,H.H.Seliger,Chemi-andbioluminescence ofﬁreﬂyluciferin,J.Am.Chem.Soc.91(1969)2178–2180.

[7]S.Beck,H.Koster,Applicationsofdioxetanechemiluminescentprobesto molecularbiology,Anal.Chem.62(1990)2258–2270.

[8]J.Wu,X.Fu,C.Xie,M.Yang,W.Fang,S.Gao,TiO2nanoparticles-enhanced

luminolchemiluminescenceanditsanalyticalapplicationsinorganophosphate pesticideimprinting,Sens.Actuators,B:Chem.160(2011)511–516. [9]K.R.Kopecky,C.Mumford,Luminescenceinthethermaldecompositionof

(6)

[10]M.Matsumoto,Advancedchemistryofdioxetane-basedchemiluminescent substratesoriginatingfrombioluminescence,J.Photochem.Photobiol.,C: Pho-tochem.Rev.5(2004)27–53.

[11]M. Matsumoto, N. Watanabe, N. Hoshiya, H.K. Ijuin, Color modulation for intramolecular charge-transfer-induced chemiluminescence of 1,2-dioxetanes,Chem.Rec.8(2008)213–228.

[12]H.Sies,Glutathioneanditsroleincellularfunctions,FreeRadicalBiol.Med.27 (1999)916–921.

[13]J.M.Estrela,A.Ortega,E.Obrador,Glutathioneincancerbiologyandtherapy, Crit.Rev.Clin.Lab.Sci.43(2006)143–181.

[14]O.Kabil,R.J.Banerjee,Redoxbiochemistryofhydrogensulﬁde,J.Biol.Chem. 285(2010)21903–21907.

[15]H.S.Jung,X.Chen,J.S.Kim,J.Yoon,Recentprogressinluminescentand col-orimetricchemosensorsfordetectionofthiols,Chem.Soc.Rev.42(2013) 6019–6031.

[16]Y.Qian,B.Yang,Y.Shen,Q.Du,L.Lin,J.Lin,H.Zhu,A BODIPY–coumarin-based selective ﬂuorescent probefor rapidly detecting hydrogensulﬁde in blood plasma and living cells,Sens. Actuators, B: Chem.182 (2013) 498–503.

[17]M.Isik,T.Ozdemir,I.S.Turan,S.Kolemen,E.U.Akkaya,Chromogenic, Fluo-rogenicsensingofbiologicalthiolsinaqueoussolutionsusingBODIPY-based reagents,Org.Lett.15(2013)216–219.

[18]Y.Yang,C.Yin,Y.Chu,H.Tong,J.Chao,F.Cheng,A.Zheng,pH-sensitive ﬂuo-rescentsalicylaldehydederivativeforselectiveimagingofhydrogensulﬁdein livingcells,Sens.Actuators,B:Chem.186(2013)212–218.

[19]C.X.Duan,Y.G.Liu,Recentadvancesinﬂuorescentprobesformonitoringof hydrogensulﬁde,Curr.Med.Chem.20(2013)2929–2937.

[20]R.Wang,Hydrogensulﬁde:thethirdgasotransmitterinbiologyandmedicine, Antioxid.RedoxSignaling12(2010)1061–1064.

[21]G.Szabó,G.Veres,T.Radovits,D.Gero,K.Módis,C.M.Gröschel,F.Horkay,M. Karck,C.Szabó,Cardioprotectiveeffectsofhydrogensulﬁde,NitricOxide25 (2011)201–210.

[22]B.L.Predmore,D.J.Lefer,Developmentofhydrogensulﬁdebasedtherapeutics forcardiovasculardisease,J.Cardiovasc.Transl.Res.3(2010)487–498. [23]R.Baskar,J.Bian,Hydrogensulﬁdegashascellgrowthregulatoryrole,Eur.J.

Pharmacol.656(2011)5–9.

[24]M.J.Wang,W.J.Cai,N.Li,Y.J.Ding,Y.Chen,Y.C.Zhu,Thehydrogensulﬁdedonor NaHSpromotesangiogenesisinaratmodelofhindlimbischemia,Antioxid. RedoxSignaling12(2010)1065–1077.

[25]C.Szabó,A.Papapetropoulos,Hydrogensulphideandangiogenesis: mecha-nismsandapplications,Br.J.Pharmacol.164(2011)853–865.

[26]Z.Ekmekci,M.D.Yilmaz,E.U.Akkaya,Amonostyryl-boradiazaindacene (BOD-IPY)derivativeascolorimetricandﬂuorescentprobeforcyanideions,Org.Lett. 10(2008)461–464.

[27]I.S.Turan,F.P.Cakmak,F.Sozmen,Highlyselectiveﬂuoridesensingvia chro-mogenicaggregationofasilyloxy-functionalizedtetraphenylethylene(TPE) derivative,TetrahedronLett.55(2014)456–459.

[28]Z.H.Liu,S.Devaraj,C.R.Yang,Y.P.Yen,Anewselectivechromogenicand ﬂuorogenic sensor for citrateion, Sens. Actuators, B:Chem. 174 (2012) 555–562.

[29]S.Atilgan,T.Ozdemir,E.U.Akkaya,AsensitiveandselectiveratiometricnearIR ﬂuorescentprobeforzincionsbasedonthedistyryl-bodipyﬂuorophore,Org. Lett.10(2008)4065–4067.

[30]C.X.Yin,F.J.Huo,P.Yang,Anion-basedchromogenicdetectingmethodfor phosphate-containingderivativesinphysiologicalcondition,Sens.Actuators, B:Chem.109(2005)291–299.

Biographies

IlkeSimsekTuranisaPh.D.studentinUNAM—NationalNanotechnologyResearch CenteratBilkentUniversity,Ankara,Turkey.SheearnedherM.Sc.degreein chem-istryfromMiddleEastTechnicalUniversity(METU),Ankarain2009andB.Sc.degree inchemistryeducationfromMiddle EastTechnicalUniversity (METU),Ankara in2007.Herresearchinterestandexperiencearedevelopmentofnovel chemi-luminescentcompounds,photodynamictherapy,molecularsensorsandmolecular logicgates.

FazliSozmenisaseniorresearchscientistinUNAM—NationalNanotechnology ResearchCenter,BilkentUniversity,Ankara,Turkey.HeearnedhisDoctoraldegree inchemistryfromAkdenizUniversity,Antalya,Turkeyin2012.HeearnedhisM.Sc. andB.Sc.degreesinchemistryfromAkdenizUniversityin2005and2002, respec-tively.Hisresearchinterestandexperiencearelightharvestingsupramolecular systems,self-assembledfunctionalsystems,molecularsensorsandmolecularlogic gates.HisPh.D.thesiswasonthesynthesisofnewBODIPYderivativesincluding ter-pyridineandphenantroline,preparationoftheirmetallosupramolecularcomplexes andenergytransfer.