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Monoalkoxy BODIPYs--a fluorophore class for bioimaging.

Courtis AM, Santos SA, Guan Y, Hendricks JA, Ghosh B, Szantai-Kis DM, Reis SA, Shah JV, Mazitschek R - Bioconjug. Chem. (2014)

Bottom Line: These novel fluorescent dyes, which we term MayaFluors, are characterized by good aqueous solubility and favorable in vitro physicochemical properties.MayaFluors are readily accessible in good yields in a one-pot, two-step approach starting from well-established BODIPY dyes, and allow for facile modification with functional groups of relevance to bioconjugate chemistry and bioorthogonal labeling.Biological profiling in living cells demonstrates excellent membrane permeability, low nonspecific binding, and lack of cytotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Center for Systems Biology and ∥Center for Human Genetic Research, Massachusetts General Hospital , 185 Cambridge Street, Boston, Massachusetts 02114, United States.

ABSTRACT
Small molecule fluorophores are indispensable tools for modern biomedical imaging techniques. In this report, we present the development of a new class of BODIPY dyes based on an alkoxy-fluoro-boron-dipyrromethene core. These novel fluorescent dyes, which we term MayaFluors, are characterized by good aqueous solubility and favorable in vitro physicochemical properties. MayaFluors are readily accessible in good yields in a one-pot, two-step approach starting from well-established BODIPY dyes, and allow for facile modification with functional groups of relevance to bioconjugate chemistry and bioorthogonal labeling. Biological profiling in living cells demonstrates excellent membrane permeability, low nonspecific binding, and lack of cytotoxicity.

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Time-dependentstability of 10, 12a–d at 1 μM and room temperature in (a) PBS (pH = 7.4)and (b) RPMI 1640 Media; (−) phenol-red; (+) 10% fetal bovineserum (FBS).
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fig3: Time-dependentstability of 10, 12a–d at 1 μM and room temperature in (a) PBS (pH = 7.4)and (b) RPMI 1640 Media; (−) phenol-red; (+) 10% fetal bovineserum (FBS).

Mentions: To further probe the persistenceof the chemical integrity of the dyes and identify fluorescent degradationproducts that would not result in reduction of overall fluorescence(Figure 3) we also monitored the stabilityof representative BODIPY derivatives over 24 h in PBS by LC-MS. Thestability data obtained at room temperature and 37 °C (SI Figures 2 and 3) demonstrate that the monoalkoxyanalogues exhibit good to very good stability. In contrast, the dimethoxyreference compound 10 was characterized by increasedhydrolysis and underwent near-quantitative degradation after 24 hincubation at 37 °C. This data stands in sharp relief to themonomethoxy derivative 12a that experienced only modestdegradation under these conditions. Importantly, monoalkoxy derivativeswith incrementally larger substituents were characterized by improvedstability displaying only minor or no hydrolysis. Detailed LC-MS analysisrevealed that both difluoro 9 and fluoro-alkoxy 12 BODIPY hydrolyze to form the common 4-fluoro-4-hydroxyBODIPY as the primary degradation product, while the formation of4-methoxy-4-hydroxy BODIPY was observed for compound 10.


Monoalkoxy BODIPYs--a fluorophore class for bioimaging.

Courtis AM, Santos SA, Guan Y, Hendricks JA, Ghosh B, Szantai-Kis DM, Reis SA, Shah JV, Mazitschek R - Bioconjug. Chem. (2014)

Time-dependentstability of 10, 12a–d at 1 μM and room temperature in (a) PBS (pH = 7.4)and (b) RPMI 1640 Media; (−) phenol-red; (+) 10% fetal bovineserum (FBS).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215867&req=5

fig3: Time-dependentstability of 10, 12a–d at 1 μM and room temperature in (a) PBS (pH = 7.4)and (b) RPMI 1640 Media; (−) phenol-red; (+) 10% fetal bovineserum (FBS).
Mentions: To further probe the persistenceof the chemical integrity of the dyes and identify fluorescent degradationproducts that would not result in reduction of overall fluorescence(Figure 3) we also monitored the stabilityof representative BODIPY derivatives over 24 h in PBS by LC-MS. Thestability data obtained at room temperature and 37 °C (SI Figures 2 and 3) demonstrate that the monoalkoxyanalogues exhibit good to very good stability. In contrast, the dimethoxyreference compound 10 was characterized by increasedhydrolysis and underwent near-quantitative degradation after 24 hincubation at 37 °C. This data stands in sharp relief to themonomethoxy derivative 12a that experienced only modestdegradation under these conditions. Importantly, monoalkoxy derivativeswith incrementally larger substituents were characterized by improvedstability displaying only minor or no hydrolysis. Detailed LC-MS analysisrevealed that both difluoro 9 and fluoro-alkoxy 12 BODIPY hydrolyze to form the common 4-fluoro-4-hydroxyBODIPY as the primary degradation product, while the formation of4-methoxy-4-hydroxy BODIPY was observed for compound 10.

Bottom Line: These novel fluorescent dyes, which we term MayaFluors, are characterized by good aqueous solubility and favorable in vitro physicochemical properties.MayaFluors are readily accessible in good yields in a one-pot, two-step approach starting from well-established BODIPY dyes, and allow for facile modification with functional groups of relevance to bioconjugate chemistry and bioorthogonal labeling.Biological profiling in living cells demonstrates excellent membrane permeability, low nonspecific binding, and lack of cytotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Center for Systems Biology and ∥Center for Human Genetic Research, Massachusetts General Hospital , 185 Cambridge Street, Boston, Massachusetts 02114, United States.

ABSTRACT
Small molecule fluorophores are indispensable tools for modern biomedical imaging techniques. In this report, we present the development of a new class of BODIPY dyes based on an alkoxy-fluoro-boron-dipyrromethene core. These novel fluorescent dyes, which we term MayaFluors, are characterized by good aqueous solubility and favorable in vitro physicochemical properties. MayaFluors are readily accessible in good yields in a one-pot, two-step approach starting from well-established BODIPY dyes, and allow for facile modification with functional groups of relevance to bioconjugate chemistry and bioorthogonal labeling. Biological profiling in living cells demonstrates excellent membrane permeability, low nonspecific binding, and lack of cytotoxicity.

Show MeSH