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ATargetableFluorescentProbeforImagingHydrogenPeroxideintheMitochondriaofLivingCellsBryanC.DickinsonandChristopherJ.Chang*DepartmentofChemistry,UniVersityofCalifornia,Berkeley,California94720ReceivedApril2,2008;E-mail:chrischang@berkeley.eduHydrogenperoxide(H2O2)isanincreasinglyrecognizedsmall-Scheme1.SynthesisandActivationofMitoPY1moleculemediatorofphysiology,aging,anddiseaseinlivingorganisms.1–6Inthisregard,aberrantproductionoraccumulationofH2O2withincellularmitochondriaovertimeduetoenviron-mentalstress(es)and/orgeneticmutation(s)isconnectedtoseriousdiseaseswhereageisariskfactor,includingcancer7andneuro-degenerativeAlzheimer’s,Parkinson’s,andHuntington’sdiseases.8,9Indeed,overexpressionandmitochondrialtargetingofcatalase,aperoxide-detoxifyingenzyme,canincreaselifespaninmousemodels.10Ontheotherhand,newerdatasuggestthatcontrolledburstsofmitochondrialH2O2canalsoservebeneficialrolesforcellsurvival,growth,differentiation,andmaintenance.3–6NewimagingmethodsthatallowvisualizationoflocalizedproductionandaccumulationofmitochondrialH2O2inlivingsamplesarepotentiallyusefulfordisentanglingthecomplexcontributionsofthisreactiveoxygenspecies(ROS)tobothhealthyanddiseasedstates.SyntheticfluorescentH2O2indicatorsthatcanbetargetedtoprecisesubcellularlocationsofferoneapproachtothisgoalanddonotrequiretransfectionliketheirproteincounterparts,11,12buttraditionalROSindicatorssuchasdihydro-rhodamine(DHR)areunchargedandhencenotpreferentiallylocalizedincellsbeforeoxidation.13Inaddition,DHRandrelateddyesarenotspecificforH2O2overotherROS.Accordingly,mitochondrial-targetedsmallmoleculesfordetectionofspecificfluorescenceincreasebyitsconversiontoMitoPY1ox,which13,14ROSremainrare,andnoneoftheprobesreportedtodatearepossessesonemajorabsorptionbandat510nm()22300M-1selectiveforHO.Wenowreportthesynthesisandapplications-122cm)andenhancedemission(λem)528nm,Φ)0.405).Kineticsofmitochondriaperoxyyellow1(MitoPY1),anewtypeofmeasurementsoftheH2O2-mediatedboronatedeprotectionwere
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