title: Hydroxylated near-infrared BODIPY fluorophores as intracellular pH sensors.
abstract: In this study, a series of new, highly sensitive BF2-chelated tetraarylazadipyrromethane dyes are synthesized and analyzed to be suitable as on/off photo-induced electron transfer modulated fluorescent sensors for determination of intracellular pH. The ethanolic solutions of the new indicators feature absorption maxima in the range of 696-700 nm and a fluorescence emission maximum at 720 nm. Molar absorptivity and fluorescence quantum yield data were determined for the studied set of aza-BODIPY indicators. These indicators have high molar absorption coefficients of ∼80,000 M(-1) cm(-1) and quantum yields (up to 18%). Corresponding pKa values of indicators are determined from absorbance and fluorescence measurements and range from 9.1 to 10.8, depending on the selective positioning of electron-donating functionalities. The excellent photostability of the aza-BODIPY indicators makes them particularly suitable for long duration measurements. The in vitro cellular staining of living tissues in PC3 cells based on the isosbestic point at pH 7.8 and pH 9.3 has been employed which shows an increase in fluorescence intensity at 800 nm with increase in pH for certain compounds and fluorescence intensity decreases at 700 nm. Therefore, the new indicators are suitable for exploitation and adaptation in a diverse range of analytical applications.
authors.affiliation: Department of Chemistry, Georgia State University, 100 Piedmont Ave SE, Atlanta, Georgia 30302-4098, USA.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Salim
authors.forename: Eric A
authors.initials: EA
authors.lastname: Owens
authors.forename: Tielong
authors.initials: T
authors.lastname: Gao
authors.forename: Jeong Heon
authors.initials: JH
authors.lastname: Lee
authors.forename: Hoon
authors.initials: H
authors.lastname: Hyun
authors.forename: Hak Soo
authors.initials: HS
authors.lastname: Choi
authors.forename: Maged
authors.initials: M
authors.lastname: Henary
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D004579:Electron Transport; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006900:Hydroxylation; D007259:Infrared Rays; D051379:Mice; D008856:Microscopy, Fluorescence; D013050:Spectrometry, Fluorescence; D014018:Tissue Distribution
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D005456:Fluorescent Dyes
references.citation: Ann Surg Oncol. 2009 Oct;16(10):2943-52
references.pmid: 19582506
references.citation: Org Biomol Chem. 2008 Jul 21;6(14):2468-80
references.pmid: 18600265
references.citation: Angew Chem Int Ed Engl. 2006 Mar 20;45(13):2016-35
references.pmid: 16518782
references.citation: Nat Biotechnol. 2005 Mar;23(3):313-20
references.pmid: 15765087
references.citation: Chem Soc Rev. 2012 Feb 7;41(3):1130-72
references.pmid: 21796324
references.citation: Anal Chem. 2012 Aug 7;84(15):6723-30
references.pmid: 22738322
references.citation: Nat Biotechnol. 2013 Feb;31(2):148-53
references.pmid: 23292608
references.citation: Org Lett. 2009 Dec 3;11(23):5386-9
references.pmid: 19883098
references.citation: Sensors (Basel). 2008 May 08;8(5):3082-3105
references.pmid: 27879867
references.citation: Org Lett. 2006 Aug 3;8(16):3493-6
references.pmid: 16869643
references.citation: Chem Rev. 2010 May 12;110(5):2709-28
references.pmid: 19831417
references.citation: Nat Biotechnol. 2010 Dec;28(12):1300-3
references.pmid: 21057497
references.citation: Org Biomol Chem. 2010 Jun 7;8(11):2517-9
references.pmid: 20390194
references.citation: Nano Lett. 2009 Jun;9(6):2354-9
references.pmid: 19422261
references.citation: Nat Biotechnol. 2001 Apr;19(4):316-7
references.pmid: 11283581
references.citation: Mol Imaging. 2010 Oct;9(5):237-55
references.pmid: 20868625
references.citation: Angew Chem Int Ed Engl. 2001 Jan 19;40(2):385-387
references.pmid: 29712397
references.citation: J Am Chem Soc. 2004 Sep 1;126(34):10619-31
references.pmid: 15327320
references.citation: Chem Commun (Camb). 2002 Sep 7;(17):1862-3
references.pmid: 12271646