All in One Stimuli-Responsive , E ffi cient Mitotracking , and Single Source White Light Emission - Roy et al. - 2021 - Unknown

《All in One Stimuli-Responsive , E ffi cient Mitotracking , and Single Source White Light Emission - Roy et al. - 2021 - Unknown》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。

pubs.acs.org/JPCLLetterAllinOne:Stimuli-Responsive,EfficientMitotracking,andSingleSourceWhiteLightEmissionBibhisanRoy,*MalluChennaReddy,GregorP.Jose,FelixC.Niemeyer,JensVoskuhl,*andParthaHazra*CiteThis:J.Phys.Chem.Lett.2021,12,1162−1168ReadOnlineACCESSMetrics&MoreArticleRecommendations*sıSupportingInformationABSTRACT:“Allinone”typeluminogens,possessingcombinedpropertiesrelatedtooptical,materials,andbiologicalimplications,areofurgentdemandtoday,mainlybecauseofthecombinedapplicationpotentialofsuchprobes.Tothebestofourknowledge,untilnow,an“allinone”typewhitelightemittertogetherwithstimuli-responsivebehaviorandhighlyefficientmitochondrial-trackingabilityhasnotbeenreportedyet.Inthiscontribution,forthefirsttime,wehaveinvestigatedapairofluminogensexhibitingwhitelightemission(CIEcoordinates:0.35,0.35(DPAEOA)and0.29,0.33(DPAPMI))withtemperature-inducedmechanochromicfeaturesofacentrosymmetricallypackedprobe(spacegroupP−1).Mostimportantly,despitebeingneutral,ourdesignedprobeDPAEOAcanspecificallyilluminatemitochondriawiththehighestPearsoncoefficientvalue(0.93),whichisrare,asalmostallthecommerciallydevelopedmitotrackersarecationicfluorophores.Thus,thisstudywillpaveanewavenueforthedesignofnextgeneration“allinone”typeorganicluminogensexhibitingpotentialapplicationsinnotableoptical,materials,andbiologicalfields.“Allinone”typenextgenerationluminophorescomprisinghighΔΨmarisesfromitsconstantoxidizationofsubstrates,optical(singlecomponentwhitelightemission),materialswhichmaintainsanexcellent“protongradient”acrossthelipid(mechanochromiccolorchange),andbiological(neutralbilayer.11Owingtothislargemembranepotentialgradient,mitotracker)implicationshavenotbeendevelopedyet.mitochondriacantakeupcationicspecies(almostallHence,thestudyofsinglecomponentwhitelightemittersmitotrackersdevelopedsofararecationic)12efficiently.(SCWLEs)withpotentialapplicationsinmaterialsscienceandCationicmitotrackersmostlysufferfrompoorphotostability1−5biologyisahottopicinrecenttimes.Typically,SCWLEs11,12underlaserirradiation.Thiscannotbeovercomebyusingrelyonmulticomponentsystems,aswhitelightemissionhigherfluorophoreconcentrations,asthismayleadto(WLE)requiressimultaneousemissionofthethreeprimarydestructiveaggregation-causedquenching(ACQ)assemblies.DownloadedviaUNIVOFCAPETOWNonMay14,2021at14:00:28(UTC).(red,green,andblue,i.e.,RGB)oratleasttwocomplementary1−3,5Inthiscontext,CTprobesarepotentialcandidatesto(yellowandblue,i.e.,YB)colors.SCWLEsoffernumerousdecisiveadvantagesovermulticomponentsystems,overcomethisandmaybeusedasnextgenerationsuchasbetterstability,exactreproducibility,andsimplemitotrackers.CTprobesareabletocreateintramolecularSeehttps://pubs.acs.org/sharingguidelinesforoptionsonhowtolegitimatelysharepublishedarticles.1−3,5partial“positive”and“negative”segmentsusingelectronrichfabricationprocesses,tonamejustafew.However,SCWLEsaredifficulttoachieveduetotheirspecificdonorsandelectrondearthacceptorsinsuitablepolarsolventrequirementsofdifferentemissionwavelengths(RGB/YB).medium.ConsideringthepresenceoflargewatercontentsininInrecentyears,afewattemptshavebeenundertakentovivotissuesandthehighpolarityindexofwater(10.2),achieveSCWLEsbasedonexcited-stateintramolecularprotonmitochondriawouldpreferablystabilizetheCTstates.Hence,67transfer(ESIPT),conformationalisomerizationprocesses,inthiscontribution;weaimtodevelopchargetransfer,89,10chargetransfer(CT),andotherexcitedstatemechanisms.photostable,whitelightemitterswithenhancedwaterOfthese,utilizationofCTmoleculesmaybepromisingtosolubilityforbioapplications.BasedonanisoindolinonecreatemultifunctionalSCWLEspossessingapplicationpoten-acceptorcore,wehavedesignedthreefeaturedcompoundstialalsoformaterials.Moreover,CTmoleculescanbeusedinvariousbiologicalapplications,includingmitochondriatrack-ing.ThisisbecausepreciselydesignedCTprobesmayhaveReceived:November24,2020thepotentialtoenterpreferablyintothecellularmitochondria,Accepted:January18,2021despitetheabsenceofpermanentcationiccharges,whichinPublished:January22,2021contraryistherequiredfeatureforthecommerciallyavailablemitotrackers.Thisattemptcanberealizedduetothelarge11membranepotential(ΔΨm)insidethemitochondria.The©2021AmericanChemicalSocietyhttps://dx.doi.org/10.1021/acs.jpclett.0c034891162J.Phys.Chem.Lett.2021,12,1162−1168

1TheJournalofPhysicalChemistryLetterspubs.acs.org/JPCLLetterbearingnodonor(EOA)orusingdiphenylamine(DPAEOA)DPAPMIinchloroform(0.29,0.33)atsimilarconcentrationsandcarbazole(CEOA)asdonors(Scheme1).(100μM).SuchsmallorganicmoleculebasedSCWLEsarerareanddifficulttoachievebasedontwocomplementarycolorScheme1.−CO2EtBasedDesignedProbesInvestigatedincombinations.Notably,ourdesignedprobeDPAEOA,whichisThisContribution(Left)andStructureof−SO2Phexhibitingwhitelightemissiveproperties,isoneofthemajor13AttachedProbes(DPAPMI)fromPreviousWorkTakendevelopmentsasan“optical”featureoutofthethreetargetedforComparisonPurpose(Right)“triad”featurestodesignan“allinone”typenextgenerationprobe.InthisLetter,oursecondnoteworthyadvancementfromthe“biological”perspectiveistheabilityofourmoleculetotrackspecificallymitochondria.Newlydevelopedpartiallywater-solubleDPAEOAwasfoundtoilluminatespecificallythemitochondriasectionofHEK293cellswithhighefficiency(Pearsoncoefficient0.93,discussedinalaterpart)despitebeinganeutralmolecule.Herein,ourthirddevelopmentfromthe“material”standpointisthemechanochromiccolorchangeofcentrosymmetricallypackedorganicprobes.Mechanicalcolorchangefromsolidstatecentrosymmetricpacked(space14groupsP−1andP21/cetc.)organicluminogensisdifficult.Alldesignedcompoundsconsistofethylacrylate(−CO2Et)ThisLetterprovidesaglimpseofmechanochromiceventsmoieties,whichprobablyisthemainreasonfortheenhancedfromcentrosymmetricpacking(spacegroupP−1)ofdesignedsolubilityinwater(0.41mM)incontrasttothehydrophobicorganicmolecules.Tothebestofourknowledge,suchan“allphenylvinylsulfone(PVS)containingprobesdescribedbefore(Scheme1).13Mostintriguingly,theflexibleDPAcontaininginone”typemoleculeexhibitinginterestingopticalandnewlydesignedDPAEOAandthepreviouslyreportedmaterialpropertiesalongwithimportantbiologicalimplicationDPAPMI13showssinglesourcepurewhitelightemissioninisnotyetexplored.Thus,webelievethatthisLetterwillacetoneorchloroform,respectively.TheconstructedCommis-providesuitableplatformstodesignnextgenerationsionInternationaledel’eclairagé(CIE,1931)coordinatesrevealluminophore,whichwillbeinterestingforresearchersworkingwhitelightemission(0.35,0.35)ofDPAEOAinacetoneandintheoptical,materialandbiologicalfields.Figure1.EmissionprofilesofDPAEOAexcitingat330nm.Thearrowbesidethelegendindicatestheorderofthepolarity.Wehaveprovidedthecuvetteemissioncolorunderthe365nmexcitationfor10μMofDPAEOAmoleculescontainingineachsample(toppanel).Fromthecuvettecolorimages,itisclearthatinhighlypolarsolventmoleculesarepoorlyemissive,i.e.,lowquantumyield.1163https://dx.doi.org/10.1021/acs.jpclett.0c03489J.Phys.Chem.Lett.2021,12,1162−1168

2TheJournalofPhysicalChemistryLetterspubs.acs.org/JPCLLetterAllthenewlydesignedmoleculesweresynthesizedbyacollectedbyexciting(FigureS3,λex=405nm)attheredendfunctionalgroupinterconversion(FGI)followedbyoxidativesideoftheabsorptionspectra(FigureS21)toavoidtheLEcyclizationofsubstitutedbenzonitrilewithethylacrylate(EA)stateexcitation.Similarly,wehaverecordedspectraofCEOAinthepresenceoftheRumetalasaprecatalyst{RuCl2(p-indifferentsolvents(Figure1),anditisalsofollowingthecymene)}2,silversalt(AgSbF6),andCu(OAc)2·H2OinaceticsametrendasthatofDPAEOA.However,thepeakpositionsacid(fordetails,seetheSupportingInformation).andshiftsofemissionspectraareslightlydifferentprobablyFirst,tochecktheelectronicfeaturesofthenewlydesignedduetothedifferentdonorabilityandlessflip-flopmotionofmolecules,DFTcalculationshavebeenundertaken(FigurethecarbazolemoietycomparedtotheDPAmoietyofS1).Forthedonorsubstitutedmolecules(DPAEOAandDPAEOA.Insummary,dualemissionalongwithdistinctCEOA),theHOMOandLUMOelectrondensitieswereintensitiesandcolorsuggestthatourmoleculesaretunableCTmostlyfoundtoresideonthedonor(DPAandcarbazole)andprobesfollowedbyLEexcitation.Moreover,theobservedlongacceptor(isoindolinone)moieties,respectively,althoughananosecondlifetimeofourdesignedprobesbothinsolutionslightoverlaponthearylringofisoindolinoneisobservedandsolidstate(FigureS25)infersthattheemissioncomingparticularlyforDPAEOA.However,webelievethatsuchaoutfromastableCTstate.smalloverlapwillminutelyaffectthecharge-transferpossibilitySinglecrystalsofDPAEOAandCEOAsuitableforX-rayfromthedonortotheacceptor.Hence,theremaybeandiffractionhavebeengrownfromequalmixturesofDCMandelectronictransitionfromthedonor(D)totheacceptor(A)MeOHatroomtemperature(crystallographicinformationhassupportingtheintramolecularchargetransfer(CT)characterbeenprovidedintheSupportingInformation).Thepackingofourdesignedmolecules,namely,DPAEOAandCEOA.analysissuggeststhatDPAEOAandCEOAbothexhibitMoreover,wehavealsocalculatedabsorptionspectraoftheantiparallelstacking,centrosymmetricP-1spacegroup,andnewlydesignedDPAEOAandCEOAprobeusingthecomplex2D“distortedherringbone”andcrossmodepacking,Minnesotafunctional(m06hf),whichisknownasthebestrespectively(Figures2,S4,andS5).Interestingly,theseprobes15functionalforTDDFTcalculations.Thecalculatedabsorp-tionprofile(FigureS26)alsoconsistsofourexperimentalabsorptionbands(FigureS21).Toverifythetheoreticalresults,wecarriedoutsolvatochromicstudies.IntheemissionprofileoftheparentEOA,onlyasinglelocallyexcited(LE)stateorFranck−Condonemissionbandat∼380−450nmwasobservedinalmostallsolvents,whichdidnotshowanyredshiftuponincreasingofthesolventpolarity(FigureS2).However,DPAEOAandCEOAshowedahigherenergyLEpeakandalowerenergyCTpeakinvarioussolvents(Figure1).DPAEOAintolueneexhibitedtwopeaks,wherethehigherenergypeak(ataround∼400nm)correspondstotheemissionfromthelocallyexcited(LE)stateandthelowerenergypeak(>500nm)isassignedtotheemissionfromtheCTstate(Figure1).ThehigherintensityoftheCTpeakcomparedtotheLEpeakmaybeexplainedashigherpopulationofCTstatecomparedtotheLEstatebasedonaflip-flopmotion(seenoteS2intheSupportingInformation)oftheDPAmoiety.BoththeseLEandCTpeaksaregettingred-shiftedwiththeincreaseinpolarity;however,theextentofred-shiftismorepronouncedinthecaseoftheCTstatecomparedtotheLEstate.Consideringthisobservation,weanticipatedthattheLEFigure2.SlippedstackedandcrossstackedpackingofDPAEOAandCEOAasobtainedbysinglecrystalX-raydiffraction.stateisalsohavingsomechargecharacter,anditalsosupportsourtheoreticalstudywhereslightoverlapbetweenHOMOandLUMOisobserved.Notably,theintensityoftheCTstateexhibitnumerousnoncovalentinteractions.Forexample,diminishedasthepolarityincreased(althoughthepopulationDPAEOAexhibitsCO···H−C(2.353Å,2.545Å),C−ofCTincreases).Here,webelievedthattheCTstateofH···π(2.875Å,2.736Å),C−H···H−C(2.388Å),andC−H···DPAEOAisstabilizedbythepolarsolventssignificantly,O(2.545Å)(FigureS6).CEOAexhibitsπ···π(3.266Å),CleadingtoadecreaseintheenergygapbetweenthisstateandH···π(2.766Å),andC−H···O(2.544Å,2.474Å).(Figurethegroundstate.Hence,nonradiativedeactivationrateS6).Weattemptedtodeterminethesenoncovalentinter-constantsbecomelarger,whichisinaccordancewiththeactionsusingHirshfeldsurfaceanalysis(NoteS1,FiguresS716,17energygaplaw.ThiscausestheefficientquenchingandS8).Theseinteractionsandpackingpatterns(centrosym-observedinpolarsolvents.Thereasonforthisisthatifthemetric/noncentrosymmetric)arethemainparameterforsolventpolarityfurtherincreased(beyondDCM),themechanochromiccolorchangeinthesolidstate.UponemissionprofileofDPAEOAconsistsofonlyared-shiftedmechanicalstress,theassociatedenergywillbereleaseddueLEpeakalongwithashoulderCTpeakat∼600nm(seeDMFtorupturingoftheseinteractionsbycreatingmetastableenergyandacetoneinFigure1).Whenthepolaritywasfurtherstates.Forexample,C−H···πandvanderWaals(H···H)increased(seeMeCNandMeOH),theemissionprofileinteractionswillreleaseanenthalpyof∼10.3and∼0.4−4kJ/18consistedofonlyLEpeak.Thisisattributedtotheveryweakmol,respectively.Despitenumerousnoncovalentinterac-emissionintensityoftheCTstateinhighlypolarsolvents,tions,thestimuli-responsivenessatroomtemperatureofwhichisalsoevidentfromtheobservedweakemissionprofileDPAEOAandCEOAishardtobeactivate.Thisismainly1164https://dx.doi.org/10.1021/acs.jpclett.0c03489J.Phys.Chem.Lett.2021,12,1162−1168

3TheJournalofPhysicalChemistryLetterspubs.acs.org/JPCLLetterFigure3.(A)EmissionspectraofDPAEOA(λex=365nm)inacetoneatdifferentconcentrations.(B)CIEcoordinatesofDPAEOAinacetoneuponexcitationat365nmatdifferentconcentrations.InsetshowsacuvetteofDPAEOAinacetoneunder365nmirradiationatconcentrationof100μM.duetothecentrosymmetricpackingassisted“zerogross”thecaseofDPAEOA,basedonthesolventdependentCIEdipolemomentand“degenerate”electronicenergystatesofdiagramofDPAPMI,itcanbeseenthatchloroformmaybe19themoleculeinthesolidstate.However,wehavepreviouslytherightsolventtoachievewhitelightemission(FigureS14).gainedexperienceofactivatingsuchcentrosymmetricallyInterestingly,aconcentrationdependentstudyofDPAPMIinpackedluminogens(spacegroupP21/candP−1)viathermallychloroformrevealedalmostpureWLE(0.29,0.33,quantum19inducedcrystalphasechanges.Hence,byutilizingouryield∼13%)(FigureS15).However,likethecaseofpreviousconcept,wehavefirstmeasureddifferentialscanningDPAEOA,theWLEofDPAPMIinchloroformisfoundtocalorimetry(DSC)(FigureS9)ofbothprobestofindthebeextremelysensitivetowardconcentrationaswellastemperatureinducedcrystalphasechanges.BasedontheDSCexcitationenergy.Forexample,at100μMconcentration,thermogram,wehaveheatedDPAEOAandCEOAat∼160DPAPMIshowedWLE(0.29,0.33)uponexcitationat365nmand∼75°C,respectively,bytakingthemonaquartzslide.(FigureS15),but,uponexcitationat395nm,thesamesampleAftercoolingtoroomtemperaturefollowedbyslightgrindingshowedyellowemission(0.42,0.45)(FigureS16).Wefoundwithaspatula,bothcompoundsshowgreentoyellowthattheWLEofDPAPMIcanbeseenbythenakedeyeovera(DPAEOA)andcyantogreen(CEOA)colorchangealongwiderangeofconcentrationsstartingfrom100to25μMwithabathochromicshiftintheemissionprofilewithrespectowingtothebalancedcontributionofLEandCTstatesintothepristinestate(FiguresS10andS11).CHCl3(FigureS15).However,atlowerconcentration(5ThedualemissionofLE(bluerange)andCT(yellowμM),DPAPMIshowednearwhiteemission(0.25,0.28)inrange)statesofthedesignedprobespromptedustochecktheCHCl3uponexcitationat365nmbutweakyellowemissionatpossibilityWLEgenerationbasedonyellow,blue(YB)395nm(FiguresS15andS16).Wehavefurthertriedtocomplementarycolorcombination.Hence,wehaveinvestedachieveWLEinthesolidstateusingpoly(methylmeth-muchefforttofindWLEinvariousmedia.Hereitispertinentacrylate)(PMMA)filmsdopedwithourprobes.AlthoughwetomentionthatthenatureofthedualemissionisfoundtobebelievethatitwillbepossibletoachieveWLEforbothhighlydependentonboththeconcentrationandpolarityoftheDPAEOAandDPAPMIinthesolidstate,astheyexhibitthesolventandontheexcitationenergy(Figures3,S12,andS13).dualLEandCTemissionslikewiseinthesolutionstate,itisTherefore,findingasuitablesolvent,concentration,andproperextremelyhardtogetthesuitablepopulationsofLEandCTexcitationenergyiscrucialtoachievewhitelightemissioninstatestoyieldWLEinpolymericfilm.Notably,itrequiresoursystem.Notably,tofindsuitablesolvent(s)forachievingmultipletrialstoachievetheexactpopulationforgettingwhiteWLE,wehaveprogressedsystematicallybasedonthelightemission.However,wehaveprovidedhereglimpsesthatobservationofconstructedsolventdependentCIEdiagramstheslightchangeofconcentration(0.25−1wt%)ofDPAPMIofDPAEOAandDPAPMI(FiguresS12andS14).Solventisabletochangeitscolorsignificantly(FigureS19).Therefore,dependentCIEstudiesofDPAEOA(FigureS13)inferthatwebelieveatasuitableweightpercent,theDPAEOAandprobablyCHCl3andacetonewillbesuitablesolventstoDPAPMIwillshowWLEinthesolidstatealso,whichremainsachievepurewhitelightunderacertainconcentration,asascopeforfuturestudy.Insummary,WLEofthismoleculeiscoordinatesofthesesolventsarefoundtoresideveryclosetoveryspecific,anditdependsonconcentration,polarity,andpurewhitelightcoordinates(0.33,0.33)intheCIEdiagramexcitationenergy.(FigureS12).Interestingly,asystematicconcentrationdepend-MitochondriaplaysmajorroleforenergycyclesbyentstudyofDPAEOAinacetonerevealedpurewhitelightproductionofATPviaaseriesofelectron-transportreactionsemission(0.35,0.35at100μM)inacetone(quantumyield∼pathways.Mitochondriaalsogeneratesreactiveoxygenspecies10%)uponexcitationat365nm(Figure3),whichwasnot(ROS),leadingthecelldeath,whichisknownasthe20achievedinchloroformat100μM(FigureS18).Incontrasttomitochondria-mediatedapoptosisprocess.Togetinsights1165https://dx.doi.org/10.1021/acs.jpclett.0c03489J.Phys.Chem.Lett.2021,12,1162−1168

4TheJournalofPhysicalChemistryLetterspubs.acs.org/JPCLLetterinthestudyofthisapoptosisprocesses,theexacttrackingofmitotrackerstainingdyes,theduallabelingofHEK293cellsmitochondriaisextremelyessential.Fromthiscontext,lightwascarriedoutusingDPAEOAandMitoTrackerRed(Figureemissiveprobesthatcanselectivelyenterandilluminatethe4B).Surprisingly,fluorescenceoftheDPAEOAisfoundtobecellularmitochondrialpartarehighlyimportant.ItisimportantcolocalizedwiththatoftheMitoTrackerRedfluorescencetomentionthattheconstantoxidizationofsubstratesin(Figure4B).Notably,thePearsoncoefficient(Pearsonmitochondriamaintainsanimpressiveprotongradientacrosscoefficient(PC)calculationprovidesastatisticalwaytothelipidbilayerwithaverylargemembranepotential(ΔΨm)quantifycolocalization,andaPCvaluecloserto1indicatesaofaround−180mV(negativeinside),whichdrivesthesignificantcolocalization)isfoundtobe0.93(FigureS20),accumulationofcationicprobespreferentiallyintheanditisthehighestvaluecomparedtoanotherrecently24mitochondrialmatrixthanontheplasmamembranewithareportedPearsoncoefficientvalue(0.90)forneutraldrug.membranepotentialof30−60mV(negativeinside).12,21AsaThisresultisintriguingasthedesignedprobedoesnotcontainresult,averylargeconcentrationofcationicprobesgetpermanentcationicchargeslikethoseofconventionalaccumulatedinsidemitochondria(nearly500-fold)thananymitotrackersavailableonthemarket.Webelievethereareotherpartofthecell.22Duetothisreason,almostallthreemajorreasonstoenterspecificallymitochondriadespitedevelopedmitotrackersarebasedoncationicfluorophoresnothavingpermanentcationicchargesofourdesignedprobe.suchasMitoTrackerRed(MTR),MitoTrackergreen(MTG),Thefirstoneisthepresenceofapendantesterarm,whichisandRhodamine123.23However,thedilutedsolutionsofwell-knowntorenderthemoleculecellpermeable,andalsoit27cationicmitotrackerssufferfrompoorphotostability.12Hence,increasesthewatersolubilityoftheprobe.Second,beingaaneutralefficient,photostable,mitotrackerisveryimportant.donor−acceptorprobe,DPAEOAwillcontainthepermanentConsideringpartialwatersolubilityandtheneutralstructureofoxidationpotentialwhichhelpsthemoleculetospecificallyourcompounds,inspiredustostudythemitochondriaimagingaccumulateatthemitochondriabearinglargemembraneusingourdesignedmolecules.Interestingly,wehaveobservedpotential(ΔΨm).NitrogenheterocycleswithN−Hbondscanimprovethemitochondrialtargetingabilityofpartialneutralthat,amongthetwodesignedprobes,onlyDPAEOAshowsan24fluorophores.exceptionalabilitytotargetmitochondriaspecifically,despiteInconclusion,wehavedevelopedandinvestigatedsmalltheirneutralstructures,whichisscarcelyreportedinthe24−26organicwhitelightemitters(CIEcoordinates:0.35,0.35literature.Notably,thisisthefirstreportontheester(DPAEOA)and0.29,0.33(DPAPMI))thatpossessbasedperfectneutralmitotracker.Interestingly,onlyDPAEOAthermoinducedmechanochromicmaterialsfeatures.MoreincubatedHEK293cells(fordetails,seetheSupportinginterestingly,oneoftheluminogens(DPAEOA)showsanInformation)arefoundtoexhibitefficientcellularuptakeexceptionalabilitytotargetspecificallymitochondriawitha(Figure4)withrespecttotheCEOAtreatedcellspossiblyduehighPearsoncoefficient(0.93),despitetheirnoncationictotheefficientrotationalrestrictioneffectoftwoarylrotorsofstructures.Thisobservationisrare,asalmostallthetheDPAEOAluminogen.Thatiswhywehaveobservedverycommerciallydevelopedmitotrackersarecationicfluoro-weakfluorescenceintensityofCEOAwhenincubatedwithphores.Tothebestofourknowledge,suchan“allinone”HEK293cells(Figure4A).Inordertocomparetheabilityoftypesinglesourcewhitelightemitterwithstimuli-responseandtrackingoftheDPAEOAmoleculewiththetraditionalspecificmitochondriatrackingabilityisnotreportedyet.Thus,webelievethisstudywillputforwardthefundamentaldevelopmentideaof“allinone”typefluorescentprobesexhibitingtheoptical,materials,andbiologicalapplications■triad.ASSOCIATEDCONTENT*sıSupportingInformationTheSupportingInformationisavailablefreeofchargeathttps://pubs.acs.org/doi/10.1021/acs.jpclett.0c03489.Experimentalsection,mechanism,synthesisandcharac-terization,NMRdata,crystallographictable,DFT,TD-DFTdata,solvatochromicdata,absorptionspectra,crystallographicfigures,Hirshfeldsurfaceanalysis,DSC,mechanochromism,temperaturedependentstudy,PXRDdata,CIEcoordinates,Pearson’scoef-ficientcalculation,aswellasnotesS1andS2(PDF)■AUTHORINFORMATIONCorrespondingAuthorsParthaHazra−DepartmentofChemistry,IndianInstituteofScienceEducationandResearch(IISER),Pune,Maharashtra411008,India;orcid.org/0000-0003-0422-1399;Email:p.hazra@iiserpune.ac.inFigure4.(A)ConfocalimagesofDMSOcontrol,DPAEOA,andBibhisanRoy−DepartmentofChemistry,IndianInstituteofCEOA.(B)OverlaymitotrackingimagesofDPAEOAalongwithScienceEducationandResearch(IISER),Pune,MaharashtraMitoTrackerRed.411008,India;FacultyofChemistry(OrganicChemistry)1166https://dx.doi.org/10.1021/acs.jpclett.0c03489J.Phys.Chem.Lett.2021,12,1162−1168

5TheJournalofPhysicalChemistryLetterspubs.acs.org/JPCLLetterandCENIDE,UniversityofDuisburg-Essen,45141Essen,(9)Yang,Y.;Lowry,M.;Schowalter,C.M.;Fakayode,S.O.;Germany;Email:bibhisan.roy@students.iiserpune.ac.in,Escobedo,J.O.;Xu,X.;Zhang,H.;Jensen,T.J.;Fronczek,F.R.;bibhisan.roy@uni-due.deWarner,I.M.;Strongin,R.M.AnOrganicWhiteLight-EmittingJensVoskuhl−FacultyofChemistry(OrganicChemistry)Fluorophore.J.Am.Chem.Soc.2006,128,14081−14092.andCENIDE,UniversityofDuisburg-Essen,45141Essen,(10)Nara,M.;Orita,R.;Ishige,R.;Ando,S.White-LightEmissionandTunableLuminescenceColorsofPolyimideCopolymersBasedGermany;Email:jens.voskuhl@uni-due.deonFRETandRoom-TemperaturePhosphorescence.ACSOmegaAuthors2020,5,14831−14841.MalluChennaReddy−DepartmentofChemistry,Indian(11)Leung,C.W.;Hong,Y.;Chen,S.;Zhao,E.;Lam,J.W.;Tang,B.Z.APhotostableAIELuminogenforSpecificMitochondrialInstituteofScienceEducationandResearch(IISER),Pune,ImagingandTracking.J.Am.Chem.Soc.2013,135,62−65.Maharashtra411008,India(12)Hou,J.-T.;Ren,W.X.;Li,K.;Seo,J.;Sharma,A.;Yu,X.-Q.;GregorP.Jose−DepartmentofBiologicalSciences,IndianKim,J.S.FluorescentBioimagingofpH:fromDesigntoApplications.InstituteofScienceEducationandResearch(IISER),Pune,Chem.Soc.Rev.2017,46,2076−2090.Maharashtra411008,India(13)Roy,B.;Reddy,M.C.;Hazra,P.DevelopingtheStructure-FelixC.Niemeyer−FacultyofChemistry(OrganicPropertyRelationshiptoDesignSolidStateMulti-StimuliResponsiveChemistry)andCENIDE,UniversityofDuisburg-Essen,MaterialsandtheirPotentialApplicationsinDifferentFields.Chem.45141Essen,GermanySci.2018,9,3592−3606.(14)Xu,B.;Li,W.;He,J.;Wu,S.;Zhu,Q.;Yang,Z.;Wu,Y.C.;Completecontactinformationisavailableat:Zhang,Y.;Jin,C.;Lu,P.Y.;Chi,Z.;Liu,S.;Xu,J.;Bryce,M.R.https://pubs.acs.org/10.1021/acs.jpclett.0c03489AchievingVeryBrightMechanoluminescencefromPurelyOrganicLuminophoreswithAggregation-inducedEmissionbyCrystalDesign.NotesChem.Sci.2016,7,5307−5312.Theauthorsdeclarenocompetingfinancialinterest.(15)Walker,M.;Harvey,A.J.A.;Sen,A.;Dessent,C.E.H.PerformanceofM06,M06-2X,andM06-HFDensityFunctionalsfor■ACKNOWLEDGMENTSConformationallyFlexibleAnionicClusters:M06FunctionalsP.H.acknowledgestheScienceandEngineeringResearchPerformBetterthanB3LYPforaModelSystemwithDispersionBoard(SERB),GovernmentofIndia(CRG/2020/00567)forandIonicHydrogen-BondingInteractions.J.Phys.Chem.A2013,financialsupport.JanBalszuweit,JustinDubbert,Subrata117,12590−12600.Nath,DietrichTönnes,andFlorianMalotkeareacknowledged(16)Koenig,M.;Bottari,G.;Brancato,G.;Barone,V.;Guldi,D.M.;fortheirhelpduringvariousexperimentalmeasurements.WeTorres,T.UnravelingthePeculiarModusOperandiofaNewClassofSolvatochromicFluorescentMolecularRotorsbySpectroscopicandareindebtedtotheanonymousreviewersfortheirsuggestions.QuantumMechanicalMethods.Chem.Sci.2013,4,2502−2511.■(17)Nitzan,A.;Mukamel,S.;Jortner,J.EnergyGapLawforREFERENCESVibrationalRelaxationofaMoleculeinaDenseMedium.J.Chem.(1)Pan,M.;Liao,W.M.;Yin,S.Y.;Sun,S.S.;Su,C.Y.Single-Phys.1975,63,200−207.PhaseWhite-Light-EmittingandPhotoluminescentColor-Tuning(18)Xie,Z.;Yang,B.;Li,F.;Cheng,G.;Liu,L.;Yang,G.;Xu,H.;CoordinationAssemblies.Chem.Rev.2018,118,8889−8935.Ye,L.;Hanif,M.;Liu,S.;Ma,D.;Ma,Y.CrossDipoleStackinginthe(2)Zhang,Y.;Miao,Y.;Song,X.;Gao,Y.;Zhang,Z.;Ye,K.;Wang,CrystalofDistyrylbenzeneDerivative:TheApproachtowardHighY.Single-Molecule-basedWhite-LightEmissiveOrganicSolidswithSolid-StateLuminescenceEfficiency.J.Am.Chem.Soc.2005,127,Molecular-Packing-DependentThermallyActivatedDelayedFluo-14152−14153.rescence.J.Phys.Chem.Lett.2017,8,4808−4813.(19)Roy,B.;Reddy,M.C.;Panja,S.N.;Hazra,P.Strategyto(3)Li,X.;Cui,J.;Ba,Q.;Zhang,Z.;Chen,S.;Yin,G.;Wang,Y.;Li,MechanicalActivationofCentrosymmetricallyPackedOrganicB.;Xiang,G.;Kim,K.S.;Xu,H.;Zhang,Z.;Wang,H.L.Luminogens.J.Phys.Chem.C2019,123,3848−3854.MultiphotoluminescencefromaTriphenylamineDerivativeandIts(20)Dickinson,B.C.;Chang,C.J.ATargetableFluorescentProbeApplicationinWhiteOrganicLight-EmittingDiodesBasedonaforImagingHydrogenPeroxideintheMitochondriaofLivingCells.J.SingleEmissiveLayer.Adv.Mater.2019,31,1900613.Am.Chem.Soc.2008,130,9638−9639.(4)Grandhi,G.K.;Viswanath,N.S.M.;Cho,H.B.;Han,J.H.;(21)Casey,J.R.;Grinstein,S.;Orlowski,J.SensorsandRegulatorsKim,S.M.;Choi,S.;Im,W.B.MechanochemistryasaGreenRoute:ofIntracellularpH.Nat.Rev.Mol.CellBiol.2010,11,50−61.Synthesis,ThermalStability,andPostsyntheticReversiblePhase(22)Murphy,M.P.Targetinglipophiliccationstomitochondria.TransformationofHighly-LuminescentCesiumCopperHalides.J.Biochim.Biophys.Acta,Bioenerg.2008,1777(7−8),1028−31.Phys.Chem.Lett.2020,11,7723−7729.(23)Zielonka,J.;Joseph,J.;Sikora,A.;Hardy,M.;Ouari,O.;(5)He,Z.;Zhao,W.;Lam,J.W.Y.;Peng,Q.;Ma,H.;Liang,G.;Vasquez-Vivar,J.;Cheng,G.;Lopez,M.;Kalyanaraman,B.Shuai,Z.;Tang,B.Z.WhiteLightEmissionfromaSingleOrganicMitochondria-TargetedTriphenylphosphonium-BasedCompounds:MoleculewithDualPhosphorescenceatRoomTemperature.Nat.Commun.2017,8,416.Syntheses,MechanismsofAction,andTherapeuticandDiagnostic(6)Tang,K.C.;Chang,M.J.;Lin,T.Y.;Pan,H.A.;Fang,T.C.;Applications.Chem.Rev.2017,117,10043−10120.Chen,K.Y.;Hung,W.Y.;Hsu,Y.H.;Chou,P.T.FineTuningthe(24)Wang,Y.;Xu,B.;Sun,R.;Xu,Y.J.;Ge,J.F.TheApplicationofEnergeticsofExcited-StateIntramolecularProtonTransfer(ESIPT):NitrogenHeterocyclesinMitochondrial-TargetingFluorescentWhiteLightGenerationinASingleESIPTSystem.J.Am.Chem.Soc.MarkerswithNeutralSkeletons.J.Mater.Chem.B2020,8,7466−2011,133,17738−17745.7474.(7)Li,B.;Li,Z.;Guo,F.;Song,J.;Jiang,X.;Wang,Y.;Gao,S.;(25)Wang,C.;Taki,M.;Sato,Y.;Tamura,Y.;Yaginuma,H.;Wang,J.;Pang,X.;Zhao,L.;Zhang,Y.RealizingEfficientSingleOkada,Y.;Yamaguchi,S.APhotostableFluorescentMarkerfortheOrganicMolecularWhiteLight-EmittingDiodesfromConforma-SuperResolutionLiveImagingoftheDynamicStructureofthetionalIsomerizationofQuinazoline-BasedEmitters.ACSAppl.Mater.MitochondrialCristae.Proc.Natl.Acad.Sci.U.S.A.2019,116,Interfaces2020,12,14233−14243.15817−15822.(8)Lei,Y.L.;Jin,Y.;Zhou,D.Y.;Gu,W.;Shi,X.B.;Liao,L.S.;Lee,(26)Grzybowski,M.;Taki,M.;Senda,K.;Sato,Y.;Ariyoshi,T.;S.T.White-LightEmittingMicrotubesofMixedOrganicCharge-Okada,Y.;Kawakami,R.;Imamura,T.;Yamaguchi,S.AHighlyTransferComplexes.Adv.Mater.2012,24,5345−51.PhotostableNear-InfraredLabelingAgentBasedonaPhospha-1167https://dx.doi.org/10.1021/acs.jpclett.0c03489J.Phys.Chem.Lett.2021,12,1162−1168

6TheJournalofPhysicalChemistryLetterspubs.acs.org/JPCLLetterrhodamineforLong-TermandDeepImaging.Angew.Chem.,Int.Ed.2018,57,10137−10141.(27)Tian,L.;Yang,Y.;Wysocki,L.M.;Arnold,A.C.;Hu,A.;Ravichandran,B.;Sternson,S.M.;Looger,L.L.;Lavis,L.D.SelectiveEsterase-esterPairforTargetingSmallMoleculeswithCellularSpecificity.Proc.Natl.Acad.Sci.U.S.A.2012,109,4756−4761.1168https://dx.doi.org/10.1021/acs.jpclett.0c03489J.Phys.Chem.Lett.2021,12,1162−1168