Abstractseries of novel highly water-soluble neutral BODIPY dyes have been obtained by functionalization of BODIPY dyes with branched oligo(ethylene glycol) methyl ether groups at positions 8, 2 and 6 or 4 and 4′. Use of an ortho-substituent group of branched oligo(ethylene glycol)methyl ether on the meso-phenyl ring of BODIPY dyes, and replacement of the fluorine atoms of BODIPY dyes at positions 4 and 4′ with methyloxy or ethynyl subunits significantly enhances fluorescence quantum yields of BODIPY dyes.BODIPY (4,4′-difluoro-4-bora-3a,4a-diaza-s-indacene) dyes have gained a great deal of attention recently because of their many distinctive and desirable properties such as high extinction coefficients, narrow absorption and emission bands, high quantum efficiencies of fluorescence, and relative insensitivity to environmental perturbations, and resistance to photobleaching. 1 Biological and medical applications of the BODIPY dyes require good water solubility and resistance to the formation of nonfluorescent dimer and higher aggregates. Reported strategies to make these dyes water soluble typically involve introduction of oligo(ethylene glycol), N,N-bis(2-hydroxyethyl) amine, carbohydrates, nucleotides, or ionic hydrophilic groups such as carboxylic acid, sulfonic acid, or ammonium groups to BODIPY dyes. 2 However, neutral water soluble BODIPY dyes have advantages over ionic ones because they avoid potential nonspecific interactions through electrostatic interactions between BODIPY dyes and proteins or other biomolecules in We hypothesize that incorporation of branched oligo(ethylene glycol)methyl ether into BODIPY dyes could effectively enhance enthalpic interactions of BODIPY dyes with water and significantly increase water solubility of BODIPY dyes, and that introduction of steric hindrance at the meso or 4-position of BODIPY dyes could significantly reduce their aggregation through π-π stacking interactions between BOIDIPY cores in aqueous solution, and considerably enhance their fluorescence quantum yields. In this letter, we have introduced branched oligo(ethylene glycol)methyl ether to the meso, 2-and 6-, and 4-positions of BODIPY dyes and demonstrated significantly enhanced fluorescence quantum yields of the new dyes (the abstract scheme). These neutral BODIPY dyes are highly water soluble because of the strong hydrophilic nature of oligo(ethylene glycol)methyl ether residues. These approaches offer very efficient ways to prepare different BODIPY dyes with emission ranging from green to deep red regions.In order to demonstrate the feasibility of using branched oligo(ethylene glycol)methyl ether to enhance the water solubility of BODIPY dyes, we first introduced branched oligo(ethylene glycol)methyl ether to BODIPY dyes at the meso position (Scheme 1).Compound 4 was prepared according to a reported procedure 3 and further brominated with PBr 3 in methylene chloride at 40 °C, affording brominated branched oligo(ethylene glycol)methyl ether (5). The benzaldehyde deriviative bearing branched oligo(ethylene g...

Four near-infrared fluorescent probes have been synthesized, characterized, and evaluated for detection of lysosomal pH inside living cells.

Deep-red emissive polymeric BODIPY dyes (polymers A and B), poly(2,6-BODIPY-ethynylene)s, were prepared by palladium-catalyzed Sonogashira polymerization of 2,6-diiodo-functionalized BODIPY monomers with 2,6-diethynyl-functionalized BODIPY monomers. Poly(2,6-BODIPY-ethynylene)s emit in the deep-red region with emission spectral maxima at around 680 nm and exhibit significant red shifts (up to 163 and 172 nm) of both absorption and emission maxima compared with their initial BODIPY dyes due to significant extension of π-conjugation. Red emissive copolymeric BODIPY dyes (polymers C, D, and E) were also prepared by palladium-catalyzed Sonogashira polymerization of a diethynylfunctionalized BODIPY monomer with 9,9-bis(6′-(hexylthio)hexyl)-2,7-diiodo-9H-fluorene, 1,4-diiodo-2,5-didecyloxybenzene, and 2,5-diiodo-3-decylthiophene, respectively. Incorporation of different band gap monomer units into poly(2,6-BODIPY-ethynylene)s resulted in copolymers with a range of emission wavelengths from 641 to 664 nm. The fluorescence lifetimes of these polymers (polymers A-D) are from 2.8 to 3.8 ns except the copolymer with thiophene moieties (polymer E), which displays a much shorter lifetime of 0.23 ns with low fluorescence quantum yield due to efficient intersystem crossing induced by the heavy atom effect of sulfur.

Linear polyacrylamide (PAAm) is modified with dopamine or nitrodopamine (PAAm-D and PAAm-ND, respectively) to evaluate the effect of nitro-group modification on the interfacial binding properties of polymer-bound catechol. Nanocomposite hydrogels are prepared by mixing PAAm-based polymers with Laponite and the viscoelastic properties of these materials are determined using oscillatory rheometry. The incorporation of a small amount of catechol (≈0.1 wt% in swollen hydrogel) drastically increases the shear moduli by 1–2 orders of magnitude over those of the catechol-free control. Additionally, PAAm-ND exhibits higher shear moduli values than PAAm-D across the whole pH range tested (pH 3.0–9.0). Based on the calculated effective crosslinking density, effective functionality, and molecular weight between crosslinks, nitro-group functionalization of dopamine results in a polymer network with increased crosslinking density and crosslinking points with higher functionality. Nitro-functionalization enhances the interfacial binding property of dopamine and increases its resistant to oxidation, which results in nanocomposite hydrogels with enhanced stiffness and a viscous dissipation property.

A highly water-soluble BODIPY dye bearing electron-rich o-diaminophenyl groups at 2,6-positions was prepared as a highly sensitive and selective fluorescent probe for detection of nitric oxide (NO) in living cells. The fluorescent probe displays an extremely weak fluorescence with fluorescence quantum yield of 0.001 in 10 mM phosphate buffer (pH 7.0) in the absence of NO as two electron-rich o-diaminophenyl groups at 2,6-positions significantly quench the fluorescence of the BODIPY dye via photoinduced electron transfer mechanism. The presence of NO in cells enhances the dye fluorescence dramatically. The fluorescent probe demonstrates excellent water solubility, membrane permeability, and compatibility with living cells for sensitive detection of NO.

Formyl groups at 6-and 2,6-positions initiated Knoevenagel reactions of the methyl groups at the 7, and 1,7-positions of 1,3,5,7-tetramethyl BODIPY dyes with aromatic aldehydes. Formation of vinyl bonds at the 7-, and 1,7-positions facilitates further Knoevenagel reactions of the methyl groups at the 3,5positions. This approach offers fast, facile and versatile ways to prepare potential novel building blocks of BODIPY dyes for conjugated oligomers, dendrimers, and highly water-soluble, near-infrared emissive sensing materials.

Three highly water-soluble near-infrared emissive polymeric BODIPY dyes (polymers A-C) were prepared by the palladium-catalyzed Suzuki polymerization of highly water-soluble 2,6-diiodo-3,5distyryl-BODIPY dyes with 1,4-phenyldiboronic acid and 2,7-bis(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)-9,9-di[1-[2-(2-methoxyethoxy)ethoxy]ethyl]fluorene, respectively. Partial replacement of fluorine subunits of BODIPY cores at 4,4-positions of polymer C with ethynyl subunits resulted in a highly water-soluble BODIPY polymeric dye (polymer D). Polymers A-D show solubility of at least 20 mg mL À1 in aqueous solution. For comparison purposes, polymers E and F were prepared by palladium-catalyzed Sonogashira polymerization of highly water-soluble 2,6-diiodo-3,5-distyryl-BODIPY dye with highly water-soluble 1,4-diethynylbenzene and 2,6-diethynyl BODIPY dye bearing branched oligo(ethylene glycol)methyl ether residues, respectively. Upon comparison, polymer E shows low solubility in aqueous solution (0.1 mg mL À1 ), whereas polymer F is almost insoluble in aqueous solution (less than 0.05 mg mL À1 ), but both are soluble in organic solvents such as chloroform, DMSO and DMF (at least 10 mg mL À1 ).

Near-infrared emissive BODIPY polymeric dye bearing cancer-homing cyclic arginine-glycine-aspartic acid (RGD) peptide residues (polymer B) was prepared by post-polymerization functionalization of BODIPY polymeric dye bearing bromo groups through tetra(ethylene glycol tethered spacers (polymer A) with thiol-functionalized RGD cancer-homing peptide through thioether bonds under a mild basic condition. Polymer B possesses excellent water solubility, good photostability, biocompatibility and resistance to nonspecific interactions to normal endothelial cells, and can efficiently detect breast tumor cells through specific cooperative binding of cancer-homing RGD peptides to αVβ3 integrins of cancer cells while its parent polymer Awith outRGD residues fails to target cancer cells.