A Concise Synthesis of the Pennsylvania Green Fluorophore and Labeling of Intracellular Targets with O6-Benzylguanine Derivatives

Mottram, Laurie F.; Maddox, Ewa; Schwab, Markus; Beaufils, Florent; Peterson, Blake R.

doi:10.1021/ol7015093

Cited by 37 publications

(31 citation statements)

References 29 publications

(57 reference statements)

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“…This high polarity confers substantial aqueous solubility, which is beneficial for some applications, such as protein labeling, but also results in low cellular permeability in assays involving living cells. Hydrophobic analogues of fluorescein such as Tokyo Green ( 2 ) [2], Pennsylvania Green ( 3 ) [3–4], and others [5] have been synthesized that replace a carboxylate with a methyl group or other less polar functionality. These hydrophobic analogues are generally more effective at penetrating cellular membranes [2,4].…”

Section: Introductionmentioning

confidence: 99%

Hydrophobic analogues of rhodamine B and rhodamine 101: potent fluorescent probes of mitochondria in living C. elegans

Mottram¹,

Forbes²,

Ackley³

et al. 2012

Beilstein J. Org. Chem.

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SummaryMitochondria undergo dynamic fusion and fission events that affect the structure and function of these critical energy-producing cellular organelles. Defects in these dynamic processes have been implicated in a wide range of human diseases including ischemia, neurodegeneration, metabolic disease, and cancer. To provide new tools for imaging of mitochondria in vivo, we synthesized novel hydrophobic analogues of the red fluorescent dyes rhodamine B and rhodamine 101 that replace the carboxylate with a methyl group. Compared to the parent compounds, methyl analogues termed HRB and HR101 exhibit slightly red-shifted absorbance and emission spectra (5–9 nm), modest reductions in molar extinction coefficent and quantum yield, and enhanced partitioning into octanol compared with aqueous buffer of 10-fold or more. Comparison of living C. elegans (nematode roundworm) animals treated with the classic fluorescent mitochondrial stains rhodamine 123, rhodamine 6G, and rhodamine B, as well as the structurally related fluorophores rhodamine 101, and basic violet 11, revealed that HRB and HR101 are the most potent mitochondrial probes, enabling imaging of mitochondrial motility, fusion, and fission in the germline and other tissues by confocal laser scanning microscopy after treatment for 2 h at concentrations as low as 100 picomolar. Because transgenes are poorly expressed in the germline of these animals, these small molecules represent superior tools for labeling dynamic mitochondria in this tissue compared with the expression of mitochondria-targeted fluorescent proteins. The high bioavailabilty of these novel fluorescent probes may facilitate the identification of agents and factors that affect diverse aspects of mitochondrial biology in vivo.

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Section: Introductionmentioning

confidence: 99%

Hydrophobic analogues of rhodamine B and rhodamine 101: potent fluorescent probes of mitochondria in living C. elegans

Mottram¹,

Forbes²,

Ackley³

et al. 2012

Beilstein J. Org. Chem.

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“…Using cobalt octacarbonyl mediated radical coupling of suitably substituted aryl iodides symmetrical benzophenones were synthesized which was further cyclized to the xanthone derivative (9). [59] Starting from compound (9), Oregon Green (7), Pennsylvania Green (8) and their derivatives were synthesized through a protection, Grignard reaction, deprotection and hydrolysis sequence (Scheme 31).…”

Section: Fluorescein Derivativesmentioning

confidence: 99%

Conformationally Restricted Triarylmethanes: Synthesis, Photophysical Studies, and Applications

2018

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Triarylmethanes, compounds in which the central carbon atom is attached to three aryl rings, have a wide variety of photophysical properties which are utilized in the dye industry and also in the development of novel fluorescent tags and biomarkers. The aryl rings attached to the central carbon atom of the parent molecule triphenylmethane can freely rotate. Bridging the aryl rings of triarylmethanes with heteroatoms or through bonds decreases the conformational flexibility enjoyed by the parent molecules. Conformationally restricted triarylmethane (CRT) molecules like 9‐arylxanthenes (oxygen bridging), 9‐arythioxanthenes (sulfur bridging), 9,10‐dihydro,9‐arylacridines (nitrogen bridging), and 9‐arylfluorenes (bridging through C–C bond) have decreased conformational flexibility and display amphihydric behavior which results in benzenoid structure and quinoid structure of these molecules. The quinoid form of these molecules displays very rich photophysical properties which are the subject of this review. These molecules also have widespread utility, and over the last decade, a number of studies have been focused on the synthesis, photophysical properties, and applications of molecules derived from this core structure. Through this review, we intend to give the readers an outlook on the different strategies employed to synthesize these molecules and also provide a broader perspective on the various intriguing properties of these molecules. The applications of these classes of molecules in diverse fields like photocatalysis, chemical biology, pharmaceutical chemistry, and bio‐imaging are discussed. Also, the areas that need to be further developed are highlighted, which may provide a further impetus in the development of this class of molecules.

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“…For these fluorescein derivatives, a carboxyl group often works well. 4,10 As such, we set out to also prepare 5-carboxy-Aarhus Green.…”

Section: Synthesis Of 5-carboxy-aarhus Greenmentioning

confidence: 99%

Aarhus green: a tetrafluoro-substituted derivative of fluorescein

Holmehave¹,

Pedersen²,

Jensen³

et al. 2015

Arkivoc

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Dedicated to Professor Michael Orfanopoulos on the occasion of his 67th birthday ‡ These authors contributed equally to this work.DOI: http://dx.doi.org/10.3998/ark.5550190.p009.011 AbstractThe synthesis and characterization of a 2',4',5',7'-tetrafluorinated derivative of fluorescein, called Aarhus Green, is reported. As with related 2',7'-difluorinated compounds, tetrafluorination of the xanthene-derived moiety makes the more fluorescent anion accessible over a larger pH range. However, in contrast to a published report, we find that fluorination in the 4' and 5' positions does not appreciably decrease the fluorescence quantum yield, φ f . Rather, Aarhus Green has a reasonably large φ f (0.79 ± 0.04). Moreover, Aarhus Green does not efficiently sensitize the production of singlet oxygen and it is photostable. Thus, tetrafluorination of the xanthene moiety in fluorescein derivatives can be a useful tool in the development of fluorescent probes.

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A Concise Synthesis of the Pennsylvania Green Fluorophore and Labeling of Intracellular Targets with O⁶-Benzylguanine Derivatives

Cited by 37 publications

References 29 publications

Hydrophobic analogues of rhodamine B and rhodamine 101: potent fluorescent probes of mitochondria in living C. elegans

Hydrophobic analogues of rhodamine B and rhodamine 101: potent fluorescent probes of mitochondria in living C. elegans

Conformationally Restricted Triarylmethanes: Synthesis, Photophysical Studies, and Applications

Aarhus green: a tetrafluoro-substituted derivative of fluorescein

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