Fluorous phthalocyanines and subphthalocyanines

Yoshinaga, Kosuke; Delage-Laurin, Léo; Swager, Timothy M.

doi:10.1142/s1088424620500182

Cited by 8 publications

(6 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There have been a handful of fluorophores synthesized over the past decade that contain greater than 50 weight % fluorine (wt% F). Fluorinated variants, deemed “fluorofluorophores”, of multiple chromophore classes have been prepared, including polycyclic aromatic hydrocarbon, coumarin, , porphyrin, perylene bisimide, rhodamine, phthalocyanine, , and BODIPY scaffolds (Figure B). Despite the high wt% F, many of these fluorophores are not soluble in perfluorocarbons, solvents that are composed of purely carbon and fluorine. − This is likely a result of the large polarizable π-systems present in chromophores, which do not interact favorably with the nonpolarizable fluorous phase. , Currently, there are no fluorophores with a λ max,em above 600 nm that are soluble in perfluorocarbons.…”

Section: Introductionmentioning

confidence: 54%

“…There have been a handful of fluorophores synthesized over the past decade that contain greater than 50 weight % fluorine (wt% F). Fluorinated variants, deemed "fluorofluorophores", 13 of multiple chromophore classes have been prepared, including polycyclic aromatic hydrocarbon, 14 coumarin, 15,16 porphyrin, 17 perylene bisimide, 18 rhodamine, 19 phthalocyanine, 20,21 and BODIPY 22 scaffolds (Figure 1B). Despite the high wt% F, many of these fluorophores are not soluble in perfluorocarbons, solvents that are composed of purely carbon and fluorine.…”

Section: ■ Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fluorous Soluble Cyanine Dyes for Visualizing Perfluorocarbons in Living Systems

et al. 2020

View full text Add to dashboard Cite

The bioorthogonal nature of perfluorocarbons provides a unique platform for introducing dynamic nano-and microdroplets into cells and organisms. To monitor the localization and deformation of the droplets, fluorous soluble fluorophores that are compatible with standard fluorescent protein markers and applicable to cells, tissues, and small organisms are necessary. Here, we introduce fluorous cyanine dyes that represent the most red-shifted fluorous soluble fluorophores to date. We study the effect of covalently appended fluorous tags on the cyanine scaffold and evaluate the changes in photophysical properties imparted by the fluorous phase. Ultimately, we showcase the utility of the fluorous soluble pentamethine cyanine dye for tracking the localization of perfluorocarbon nanoemulsions in macrophage cells and for measurements of mechanical forces in multicellular spheroids and zebrafish embryonic tissues. These studies demonstrate that the red shifted cyanine dyes offer spectral flexibility in multiplexed imaging experiments and enhanced precision in force measurements.

show abstract

Section: Introductionmentioning

confidence: 54%

Section: ■ Introductionmentioning

confidence: 99%

Fluorous Soluble Cyanine Dyes for Visualizing Perfluorocarbons in Living Systems

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Similar results have been reported for fluorous phthalocyanines (F-PCs) and subphthalocyanines (F-SubPCs). Non-planar F-SubPCs with a 14 π-electron system showed improved solubility in fluorous solvents compared to almost insoluble planar F-PCs with an 18 π-electron system despite nearly identical values of 52-59 wt% F [31]. These findings indicate that alteration of planarity improves drug solubility in fluorous solvents.…”

Section: Solubilitymentioning

confidence: 80%

Perfluorocarbon Nanoemulsions with Fluorous Chlorin-Type Photosensitizers for Antitumor Photodynamic Therapy in Hypoxia

Tuan

Guseva

Ataeva

et al. 2023

IJMS

View full text Add to dashboard Cite

The efficacy of photodynamic therapy (PDT) strictly depends on the availability of molecular oxygen to trigger the light-induced generation of reactive species. Fluorocarbons have an increased ability to dissolve oxygen and are attractive tools for gas delivery. We synthesized three fluorous derivatives of chlorin with peripheral polyfluoroalkyl substituents. These compounds were used as precursors for preparing nanoemulsions with perfluorodecalin as an oxygen depot. Therefore, our formulations contained hydrophobic photosensitizers capable of absorbing monochromatic light in the long wavelength region and the oxygen carrier. These modifications did not alter the photosensitizing characteristics of chlorin such as the generation of singlet oxygen, the major cytocidal species in PDT. Emulsions readily entered HCT116 colon carcinoma cells and accumulated largely in mitochondria. Illumination of cells loaded with emulsions rapidly caused peroxidation of lipids and the loss of the plasma membrane integrity (photonecrosis). Most importantly, in PDT settings, emulsions potently sensitized cells cultured under prolonged (8 weeks) hypoxia as well as cells after oxygen depletion with sodium sulfite (acute hypoxia). The photodamaging potency of emulsions in hypoxia was significantly more pronounced compared to emulsion-free counterparts. Considering a negligible dark cytotoxicity, our materials emerge as efficient and biocompatible instruments for PDT-assisted eradication of hypoxic cells.

show abstract

“…36 Increased solubility of fluorophores in the fluorous phase should produce brighter NEs, providing that quenching by dye stacking can be avoided. "Fluorofluorophores" involving dye modification with perfluoroalkyl substituents has been applied to cyanines, 37 rhodamines, 38 phthalocyanine, 39 BODIPY, 40 and many others (Figure 10). An exemplary application using these bright dyes is cryo-fluorescence tomography (CFT).…”

Section: Fluorous Dyesmentioning

confidence: 99%

Emergent Fluorous Molecules and Their Uses in Molecular Imaging

2021

View full text Add to dashboard Cite

Metrics & More Article RecommendationsCONSPECTUS: This Account summarizes recent advances in the chemistry of fluorocarbon nanoemulsion (FC NE) functionalization. We describe new families of fluorous molecules, such as chelators, fluorophores, and peptides, that are soluble in FC oils. These materials have helped transform the field of in vivo molecular imaging by enabling sensitive and cell-specific imaging using magnetic resonance imaging (MRI), positron emission tomography (PET), and fluorescence detection. FC emulsions, historically considered for artificial blood substitutes, are routinely used for ultrasound imaging in clinic and have a proven safety profile and a well-characterized biodistribution and pharmacokinetics. The inertness of fluorocarbons contributes to their low toxicity but makes functionalization difficult. The high electronegativity of fluorine imparts very low cohesive energy density and Lewis basicity to heavily fluorinated compounds, making dissolution of metal ions and organic molecules challenging. Functionalization is further complicated by colloidal instability toward heat and pH, as well as limited availability of biocompatible surfactants.We have devised new fluorous chelators that overcome solubility barriers and are able to bind a range of metal ions with high thermodynamic stability and biocompatibility. NE harboring chelators in the fluorous phase are a powerful platform for the development of multimodal imaging agents. These compositions rapidly capture metal ions added to the aqueous phase, thereby functionalizing NEs in useful ways. For example, Fe 3+ encapsulation imparts a strong paramagnetic relaxation effect on 19 F T 1 that dramatically accelerates 19 F MRI data acquisition times and hence sensitivity in cell tracking applications. Alternatively, 89 Zr encapsulation creates a sensitive and versatile PET probe for inflammatory macrophage detection. Adding lanthanides, such as Eu 3+ , renders NE luminescent. Beyond chelators, this Account further covers our progress in formulating NEs with fluorophores, such as cyanine or BODIPY dyes, with their utility demonstrated in fluorescence imaging, biosensing, flow cytometry and histology. Fluorous dyes soluble in FC oils are also key enablers for nascent whole-body imaging technologies such as cryo-fluorescence tomography (CFT). Additionally, fluorous cell-penetrating peptides inserted on the NE surface increase the uptake of NE by ∼8fold in weakly phagocytic stem cells and lymphocytes used in immunotherapy, resulting in significant leaps in detection sensitivity in vivo.

show abstract

Fluorous phthalocyanines and subphthalocyanines

Cited by 8 publications

References 36 publications

Fluorous Soluble Cyanine Dyes for Visualizing Perfluorocarbons in Living Systems

Fluorous Soluble Cyanine Dyes for Visualizing Perfluorocarbons in Living Systems

Perfluorocarbon Nanoemulsions with Fluorous Chlorin-Type Photosensitizers for Antitumor Photodynamic Therapy in Hypoxia

Emergent Fluorous Molecules and Their Uses in Molecular Imaging

Contact Info

Product

Resources

About