-Bridged BODIPY Dimers: Exploring the Electron-Rich and Electron-Poor Coupling Limit via Pyrrole and Pyridine Annulation.

facile access to -heteroaryl-fused bis-BODIPY scaffolds has been developed. A BODIPY dimer with an α,α-amine linker serves as a starting material to obtain pyrrole- and pyridine-fused BODIPYs, either by direct oxidation or by oxidative condensation with an aldehyde building block. Both species mark antipodal conjugative coupling conditions that result in distinct spectral outcomes.

A BOIMPY Dye Enables Multi-Photoinduced Electron Transfer Catalysis: Reaching Super-Reducing Properties.

An established concept to create radical intermediates is photoexcitation of a catalyst to a higher energy intermediate, subsequently leading to a photoinduced electron transfer (PET) with a reaction partner. The known concept of consecutive photoinduced electron transfer (con-PET) leads to catalytically active species even higher in energy by the uptake of two photons. Generally speaking, increased photon uptake leads to a more potent reductant.

Linear Amine-Linked Oligo-BODIPYs: Convergent Access via Buchwald-Hartwig Coupling.

A convergent route toward nitrogen-bridged BODIPY oligomers has been developed. The synthetic key step is a Buchwald-Hartwig cross-coupling reaction of an α-amino-BODIPY and the respective halide. Not only does the selective synthesis provide control of the oligomer size, but the facile preparative procedure also enables easy access to these types of dyes.

Transforming Dyes into Fluorophores: Exciton-Induced Emission with Chain-like Oligo-BODIPY Superstructures.

Herein we present a systematic study demonstrating to which extent exciton formation can amplify fluorescence based on a series of ethylene-bridged oligo-BODIPYs. A set of non- and weakly fluorescent BODIPY motifs was selected and transformed into discrete, chain-like oligomers by linkage via a flexible ethylene tether. The prepared superstructures constitute excitonically active entities with non-conjugated, Coulomb-coupled oscillators.

NIR-emitting benzene-fused oligo-BODIPYs for bioimaging.

Near-infrared (NIR) fluorophores are emerging tools for biophotonics because of their reduced scattering, increased tissue penetration and low phototoxicity. However, the library of NIR fluorophores is still limited. Here, we report the NIR fluorescence of two benzene-fused oligo-BODIPYs in their hexameric (H) and octameric (O) forms.

Ultrafast Resonance Energy Transfer in Ethylene-Bridged BODIPY Heterooligomers: From Frenkel to Förster Coupling Limit.

A series of distinct BODIPY heterooligomers (dyads, triads, and tetrads) comprising a variable number of typical BODIPY monomers and a terminal red-emitting styryl-equipped species acting as an energy sink was prepared and subjected to computational and photophysical investigations in solvent media. An ethylene tether between the single monomeric units provides a unique foldameric system, setting the stage for a systematic study of excitation energy transfer processes (EET) on the basis of nonconjugated oscillators. The influence of stabilizing β-ethyl substituents on conformational space and the disorder of site energies and electronic couplings was addressed.

GlycoBODIPYs: Sugars Serving as a Natural Stock for Water-soluble Fluorescent Probes of Complex Chiral Morphology.

A range of unprocessed, reducing sugar substrates (mono-, di-, and trisaccharides) is shown to take part in a straightforward four-step synthetic route to water-soluble, uncharged BODIPY derivatives with unimpaired chiral integrity and high fluorescence efficiency. A wide compatibility with several postfunctionalizations is demonstrated, thus suggesting a universal utility of the multifunctional glycoconjugates, which we call GlycoBODIPYs. Knoevenagel condensations are able to promote a red-shift in the spectra, thereby furnishing strongly fluorescent red and far-red glycoconjugates of high hydrophilicity.

One-Pot Strategy for Symmetrical and Unsymmetrical BOIMPY Fluorophores.

We report the improved direct access to red-emitting BOIMPY fluorophores (λ ≈ 600 nm) via a simple one-pot approach. Our method starts from easily available benzimidazole-2-carboxylic acids and not only greatly improves the overall yields but also saves both costly reagents and time. In addition, the method facilitates the synthesis of novel unsymmetrical BOIMPY motifs.

Photoactivatable Fluorophore for Stimulated Emission Depletion (STED) Microscopy and Bioconjugation Technique for Hydrophobic Labels.

The use of photoactivatable dyes in STED microscopy has so far been limited by two-photon activation through the STED beam and by the fact that photoactivatable dyes are poorly solvable in water. Herein, we report ONB-2SiR, a fluorophore that can be both photoactivated in the UV and specifically de-excited by STED at 775 nm. Likewise, we introduce a conjugation and purification protocol to effectively label primary and secondary antibodies with moderately water-soluble dyes.

Extended Benzene-Fused Oligo-BODIPYs: In Three Steps to a Series of Large, Arc-Shaped, Near-Infrared Dyes.

We present a straightforward, three-step synthesis engaging an oligomerization and subsequent one-pot oxidation step to form fully conjugated, benzene-fused oligo-BODIPYs from simple BODIPY precursors. FeCl serves as an efficient, bifunctional oxidant for a (multiple) cyclization/desaturation process, applied to ethylene-bridged dimeric, trimeric and oligomeric species to transform linking ethano units into stiff benzene fusions between unsubstituted β-positions of each BODIPY unit. The structural integrity was verified by X-ray crystallography, and all target compounds were studied in detail by photophysical, electrochemical and computational means.

Differential recognition of lipid domains by two Gb3-binding lectins.

The two lectins LecA from Pseudomonas aeruginosa and the B-subunit of Shiga toxin from Shigella dysenteriae (StxB) share the glycosphingolipid globotriaosylceramide (Gb3) as receptor. Counterintuitively, we found that LecA and StxB segregated into different domains after recognizing Gb3 at the plasma membrane of cells. We hypothesized that the orientation of the carbohydrate head group of Gb3 embedded in the lipid bilayer differentially influences LecA and StxB binding.

Shiga toxin binding alters lipid packing and the domain structure of Gb-containing membranes: a solid-state NMR study.

We studied the influence of globotriaosylceramide (Gb3) lipid molecules on the properties of phospholipid membranes composed of a liquid ordered (lo)/liquid disordered (ld) phase separated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/N-palmitoyl-d-erythro-sphingosylphosphorylcholine (PSM)/cholesterol mixture (40/35/20, mol/mol/mol) supplemented with 5 mol% of either short acyl chain palmitoyl-Gb3 or long acyl chain lignoceryl-Gb3 using 2H solid-state NMR spectroscopy. To this end, both globotriaosylceramides were chemically synthesized featuring a perdeuterated lipid acyl chain. The solid-state 2H NMR spectra support the phase separation into a POPC-rich ld phase and a PSM/cholesterol-rich lo phase.

New Dyes Based on Extended Fulvene Motifs: Synthesis through Redox Reactions of Naphthoquinones with Donor-Acceptor Cyclopropanes and Their Spectroelectrochemical Behavior.

Novel dyes based on extended fulvene motifs are reported. The carbon skeleton was generated by a catalyzed addition of donor-acceptor cyclopropanes to naphthoquinone. The hydroxy group at the central ring of the tricyclic fulvene motif was converted into the triflate, which reacted efficiently with a wide range of nucleophiles, resulting in substitution and thereby providing new derivatives.

Exploring the π-System of the (Aza-)BOIMPY Scaffold: Electron-Rich Pyrrole Moieties Working in Concert with Electron-Depleted Meso-Positions.

The recently introduced (Aza-)BOIMPY scaffold (bis(borondifluoride)-8-imidazodipyrromethene) is equipped with electron-rich β-alkoxy/α-aryl-substituted pyrrole moieties to saturate the highly electron-depleted, benzimidazole- and tetrazole-bearing meso-positions of the (Aza-)BOIMPY core. The established push-pull system gives rise to a series of compact, red- and near-infrared absorbing dyes and fluorophores with inverted high polarity compared to the native borondipyrromethene motif. The extent of conjugation of the pyrrolic α-aryl fragments with the dipyrrin core is studied by density functional theory (DFT) computations and correlated with observed red-shifts, vibronic progressions, and emission properties.

Aza-BOIMPYs: A Tetrazole Auxochrome for Highly Red-Emissive Dipyrromethene-Based Fluorophores.

A structural derivative of the recently designed BOIMPY motif is introduced; this derivative engages a meso tetrazole moiety and a dipyrromethene scaffold in a twofold BF -coordination scheme. A one-pot synthesis allows the isolation of unusual dipyrro-perazafulvene precursors and subsequent access to nonfluorescent mono-BF and fluorescent bis-BF species. The novel fluorophore, denoted Aza-BOIMPY, is highly emissive (Φ up to 0.

Ethylene-Bridged Oligo-BODIPYs: Access to Intramolecular J-Aggregates and Superfluorophores.

A versatile and rapid access to various chain lengths of ethylene-bridged BODIPY motifs was discovered. Corresponding oligomers comprising up to eight monomeric units were studied with respect to their microstructures by photophysical, X-ray crystallographic, and computational means. The investigation of three different dipyrrin cores revealed a crucial dependence on the substitution pattern of the core, whereas the nature of the meso-periphery is less critical.

Gb Glycosphingolipids with Fluorescent Oligoene Fatty Acids: Synthesis and Phase Behavior in Model Membranes.

Glycosphingolipids are involved in a number of physiological and pathophysiological processes, and they serve as receptors for a variety of bacterial toxins and viruses. To investigate their function in lipid membranes, fluorescently labeled glycosphingolipids are highly desirable. Herein, a synthetic route to access Gb glycosphingolipids with fluorescently labeled fatty acids, consisting of pentaene and hexaene moieties either at the terminus or in the middle of the acyl chain, has been developed.

Reactions of Donor-Acceptor Cyclopropanes with Naphthoquinones: Redox and Lewis Acid Catalysis Working in Concert.

Reactions of 2-arylcyclopropane dicarboxylates with naphthoquinones are reported. The key feature was the use of catalytic amounts of SnCl , which acts as both an electron donor and a Lewis acid. By an in situ umpolung of naphthoquinone the formerly electrophilic species is converted into a nucleophile that is able to trigger the ring-opening of the three-membered ring with formation of a new C-C bond.

Decorated BODIPY Fluorophores and Thiol-Reactive Fluorescence Probes by an Aldol Addition.

A novel entry to meso-decorated BODIPY motifs on the basis of an unusual aldol-type addition with diethyl ketomalonate is reported. The evolving β-hydroxyl group can be optionally eliminated, which suppresses the fluorescence of the BODIPY core by attachment of a π-electronically coupled methylidene malonate unit. This unit serves as a versatile, highly electrophilic acceptor platform for various nucleophilic additions.

Benzothiadiazole oligoene fatty acids: fluorescent dyes with large Stokes shifts.

Herein, we report on the synthesis and characterization of novel fluorescent fatty acids with large Stokes shifts. Three examples consisting of the same number of carbon atoms and thus of similar chain length are presented differing in their degree of unsaturation. As major fluorogenic contributor at the terminus benzo[][1,2,5]thiadiazole was used.

BOIMPYs: Rapid Access to a Family of Red-Emissive Fluorophores and NIR Dyes.

A fundamental, highly fluorescent, and easily accessible scaffold derived from the BODIPY core is reported. The use of benzimidazole as a bridging ligand at the meso position enables the binding of two BF units to provide sufficient rigidity and enhanced electron-withdrawing strength. Absorption and emission events thus take place in the red (λ≈600 nm); the fluorescence quantum yields can reach unity (0.

2-Hydroxy Fatty Acid Enantiomers of Gb3 Impact Shiga Toxin Binding and Membrane Organization.

Shiga toxin subunit B (STxB) binding to its cellular receptor Gb3 leads to the formation of protein-lipid clusters and bending of the membrane. A newly developed synthetic route allowed synthesizing the biologically most relevant Gb3-C24:1 2OH species with both, the natural (Gb3-R) as well as the unnatural (Gb3-S) configuration of the 2OH group. The derivatives bind STxB with identical nanomolar affinity, while the propensity to induce membrane tubules in giant unilamellar vesicles is more pronounced for Gb3-S.

Fluorescent penta- and hexaene fatty acids by a Wittig-Horner/elimination strategy.

Molecular fluorescent probes have revolutionized biochemical and biophysical studies in the last decades, but with regard to lipids there has been a lack of combining the slim shape of saturated acyl chains with fluorescent properties. Our strategy to pentaene and hexaene fatty acids builds upon commercially available 4-(E)-decenal, which is subjected to a Wittig-Horner reaction after chlorination in α-position. DBU-mediated β-elimination of HCl proceeding the olefination establishes a highly conjugated system to which a salt-free Wittig reaction adds a final double bond leading to a good (Z)-selectivity of 83-86%.