Monoalkoxy BODIPYs—A Fluorophore Class for Bioimaging

Courtis, Alexandra M.; Santos, Sofia A.; Guan, Yalin; Hendricks, J. Adam; Ghosh, Balaram; Szantai‐Kis, D. Miklos; Reis, Surya A.; Shah, Jagesh V.; Mazitschek, Ralph

doi:10.1021/bc400575w

Cited by 75 publications

(61 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…19,20 The original work done on alkoxy-substituted BODIPYs discovered that increasingly larger substituents were less prone to hydrolysis and displayed improved stability. 20 We selected the commercially available 3-hydroxycyclobutanecarboxylic acid as a suitable linker for its increased size compared to the original glycol-BODIPY derivatives. 20 Furthermore, the acid provides a synthetic handle for DFO conjugation.…”

Section: Resultsmentioning

confidence: 99%

Bioorthogonal Fluorophore Linked DFO—Technology Enabling Facile Chelator Quantification and Multimodal Imaging of Antibodies

et al. 2015

View full text Add to dashboard Cite

Herein we describe the development and application of a bioorthogonal fluorogenic chelate linker that can be used for facile creation of labeled imaging agents. The chelate linker is based on the trans-cyclooctene(TCO)-tetrazine(Tz) chemistry platform and incorporates deferoxamine (DFO) as a 89Zr PET tracer and a BODIPY fluorophore for multimodal imaging. The rapid (<3 min) ligation between mAb-TCO and Tz-BODIPY-DFO chelator is monitored using fluorescence and allows for determination of labeling completion. Utilizing BODIPY as the linker between mAb and DFO facilitates in chelator quantification using spectrophotometry, allowing for an alternative to traditional methods (mass and isotope dilution assay). Radiolabeling with 89Zr to form 89Zr-DFO-BODIPY-trastuzumab was found to be quantitative after incubation at room temperature for 1 h (1.5 mCi/mg specific activity). The cell binding assay using HER2+ (BT474) and HER2- (BT20) cell lines showed significant binding to 89Zr-DFO-BODIPY-trastuzumab (6.45 ± 1.87% in BT474 versus 1.47 ± 0.39% in BT20). In vivo PET imaging of mice bearing BT20 or BT474 xenografts with 89Zr-DFO-BODIPY-trastuzumab showed high tumor conspicuity, and biodistribution confirmed excellent, specific probe uptake of 237.3 ± 14.5% ID/g in BT474 xenografts compared to low, nonspecific probe uptake in BT20 xenografts (16.4 ± 5.6% ID/g) 96 h p.i. . Ex vivo fluorescence (465ex/520em) of selected tissues confirmed superb target localization and persistence of the fluorescence of 89Zr-DFO-BODIPY-trastuzumab. The described platform is universally adaptable for simple antibody labeling.

show abstract

Section: Resultsmentioning

confidence: 99%

Bioorthogonal Fluorophore Linked DFO—Technology Enabling Facile Chelator Quantification and Multimodal Imaging of Antibodies

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Difluoroboron complexes [1][2][3][4] are attractive targets in research and development of materials for opto-electronic devices [5][6][7] and in biomedicinal applications [3,[8][9][10][11][12][13][14] as they possess electron-accepting properties and strong fluorescence with high quantum yields. However most of the reported difluoroboron complexes show very small stokes shifts and hardly show any solid state fluorescence.…”

Section: Introductionmentioning

confidence: 99%

Fluorescent difluoroboron-curcumin analogs: An investigation of the electronic structures and photophysical properties

Margar

Rhyman

Ramasami

et al. 2016

Spectrochimica Acta Part A: Molecular and Biomolecular Spectros

View full text Add to dashboard Cite

“…20 On the other hand, the activation of BODIPYs with TMSOTf followed by reaction with an alcohol has only been recently investigated for the synthesis of mono-4-alkoxy-BODIPYs; the reported conditions use 5 equiv of TMSOTf followed by 100 equiv of alcohol and 10 equiv of DIPEA. 32 We modified this method and extended it to the preparation of 4,4-dialkoxy-BODIPYs, inspired by a procedure reported for boron functionalization of subphthalocyanines. 33 The optimized procedure uses 2.5 equiv (rather than 5 equiv) of TMSOTf in toluene, followed by addition of 5 equiv (rather than 100 equiv) of alcohol and 5 equiv of DIPEA (method C, Scheme 1); the smaller amount of nucleophile used in this procedure facilitates the purification and isolation of the products.…”

Section: ■ Introductionmentioning

confidence: 99%

Synthesis and Reactivity of 4,4-Dialkoxy-BODIPYs: An Experimental and Computational Study

et al. 2015

View full text Add to dashboard Cite

A series of boron-disubstituted O-BODIPYs were synthesized, and their structures and spectroscopic properties were investigated using both computational and experimental methods. Three methods were investigated for the preparation of 4,4-dimethoxy-BODIPYs bearing electron-donating or electron-withdrawing 8-aryl groups: method A employs refluxing in the presence of NaOMe/MeOH, method B uses AlCl3 in refluxing dichloromethane followed by addition of methanol as nucleophile, and method C involves activation of the BODIPYs using TMSOTf in refluxing toluene followed by addition of methanol. The yields obtained depend on the method used and the structure of the starting BODIPYs; for example, 1a and 3a were most efficiently prepared using method C (98 and 70%, respectively), while 2a was best prepared by method A (50%). Methods B and C were employed for the synthesis of seven new 4,4-dialkoxy-BODIPYs. 4,4-Dipropargyloxy-BODIPY 1e reacted under Cu(I)-catalyzed alkyne-azide Huisgen cycloaddition conditions to produce 4,4-bis(1,2,3-triazole)-BODIPY 4 in 78% yield. The substitution of the fluorides for alkoxy groups on the BODIPYs had no significant effect on the absorption and emission wavelengths but altered their fluorescence quantum yields. Among this series of dialkoxy-BODIPYs, the 4,4-dipropargyloxy 1e and its corresponding bis(1,2,3-triazole) 4 show the largest quantum yields in toluene and THF, respectively.

show abstract

Monoalkoxy BODIPYs—A Fluorophore Class for Bioimaging

Cited by 75 publications

References 36 publications

Bioorthogonal Fluorophore Linked DFO—Technology Enabling Facile Chelator Quantification and Multimodal Imaging of Antibodies

Bioorthogonal Fluorophore Linked DFO—Technology Enabling Facile Chelator Quantification and Multimodal Imaging of Antibodies

Fluorescent difluoroboron-curcumin analogs: An investigation of the electronic structures and photophysical properties

Synthesis and Reactivity of 4,4-Dialkoxy-BODIPYs: An Experimental and Computational Study

Contact Info

Product

Resources

About