Silver-Mediated Methoxycarbonyltetrafluoroethylation of Arenes

In the presence of silver(I) fluoride, highly fluorinated olefins react readily under solvent-free conditions with arenes via CH-substitution. This transformation could be used to synthesize various methoxycarbonyltetrafluoroethylated aromatic triazenes and anisoles under high functional group tolerance. The method could be applied to the synthesis of a formal fluorinated bioisostere of the NSAID flurbiprofen. To the best of our knowledge, this is the first example which uses highly fluorinated olefins for the perfluoroalkylation of aromatic substrates

Site-Specific Conjugation of Peptides and Proteins via Rebridging of Disulfide Bonds Using the Thiol–Yne Coupling Reaction

Herein, we describe an extension of our previously reported photomediated disulfide rebridging methodology to the conjugation of peptides and proteins. The methodology proved to be reproducible with various alkynes and different peptides. This study includes the first rebridging of the disulfide bond of a peptide through a thiol–yne reaction with a cyclooctyne. In all cases, the rebridging was proven by MS analyses and confirmed by the absence of olefinic protons on ¹H NMR spectra of the resulting products. Finally, this one-pot reduction thiol–yne conjugation was successfully applied to an antibody Fab fragment with a promising conversion, which set a good ground for the future syntheses of new protein and antibody conjugates

Photophysical Properties and Synthesis of New Dye–Cyclooctyne Conjugates for Multicolor and Advanced Microscopy

Cyclooctyne conjugates with fluorophores are often used for bioorthogonal labeling in cells and tissues. However, no comprehensive library of one cyclooctyne core structure with different fluorescent dyes spanning the whole visible spectrum up to the NIR had been described so far. Hence, we synthesized and evaluated one cyclooctyne core structure which is easily accessible for the attachment of different dyes for multicolor imaging, FRET analysis, and study of metabolism in vivo. For these reasons we developed an easy one step synthesis starting from a known cyclooctyne. In combination with NHS-activated dyes, the cyclooctyne reacted to the dye DAB-MFCO conjugates within only 1–2 h at room temperature with high yields. We created conjugates with dyes that have high brightness and are bleaching stable with wavelengths from green to NIR. The ability to label glycans on cell surfaces was tested. All dye DAB-MFCO conjugates undergo click reactions on azide functionalized glycan structures with satisfactory photophysical properties. In total, seven different dye DAB-MFCO conjugates were synthesized; their photophysical properties and suitability for click labeling in biological applications were evaluated, making them suitable for single molecule and high resolution measurements

<i>ortho</i>-Perfluoroalkylation and Ethoxycarbonyldifluoromethylation of Aromatic Triazenes

A robust protocol for perfluoroalkylation and ethoxycarbonyldifluoromethylation of functionalized aromatic triazenes is described. Using silver­(I)-fluoride and different fluorinated (tri­methyl)­silyl substituted species, it was possible to synthesize various <i>ortho</i>-fluorinated triazenes in good yields via simple <i>CH</i>-substitution. Initial reactions under solvent-free (neat) conditions indicate a stabilizing interaction between “AgR_f” and the triazene moiety, which may be responsible for the good yields and regioselectivity. The transformation possibilities of the triazene moiety make these reactions interesting for the synthesis of fluorinated building blocks. In addition, quantum chemical calculations suggest that the stabilization of the radical intermediate in the <i>ortho</i>-position is distinctly more favored for aromatic triazenes than for other aromatic substrates

How the Quantum Efficiency of a Highly Emissive Binuclear Copper Complex Is Enhanced by Changing the Processing Solvent

Polymorphism is often linked to the choice of processing solvents. Packing effects or the preference of one certain conformer as possible causes of this phenomenon are strongly dependent on solvents and especially on their polarity. Even in amorphous solids, the microstructure can be controlled by the choice of solvents. Polymorphs or amorphous solids featuring different packing densities can exhibit different properties in terms of stability or optical effects. The influence of these effects on a binuclear, strongly luminescent copper­(I) complex was investigated. Many possible applications for luminescent, amorphous coordination compounds, such as organic light-emitting diodes, sensors, and organic lasers, rely on photophysical properties like quantum efficiency to be repeatable. The effect of processing solvents in this context is often underestimated, but very relevant for utilization in device manufacturing and should therefore be understood more deeply. In this work, theoretical derivations, DFT calculations, X-ray-diffraction, photoluminescence spectroscopy, and the time-dependent single-photon-counting-technique (TDSPC) were used to understand this phenomenon more deeply. The influence of five different solvents on Cu₂I₂(MePyrPHOS)₃ was probed. This resulted in a modulation of the photoluminescence quantum yield ϕ between 0.5 and 0.9 in amorphous solid state. A new polymorph of the material with slightly reduced values for ϕ has been identified. The reduced efficiency could be correlated with a higher porosity and a reduced packing density. Dense packing reduces nonradiative decay by geometrical fixation and thus increases the quantum efficiency. The existence of similar effects on aluminum and iridium compounds has been confirmed by application of different processing solvents on Alq₃ and Ir­(ppy)₃. These results show that a tuning of the efficiency of a emissive metal complexes by choosing a proper processing solvent is possible. If highly efficient materials for practical applications are desired, an evaluation of multiple solvents has to be considered

Copper(I) Complexes Based on Five-Membered P^∧N Heterocycles: Structural Diversity Linked to Exciting Luminescence Properties

Bridging P^∧N ligands bearing five-membered heterocyclic moieties such as tetrazoles, 1,2,4-triazoles, oxadiazoles, thiadiazoles, and oxazoles have been investigated regarding their complexation behavior with copper­(I) iodide as metal salts. Different complex structures were found, depending either on the ligand itself or on the ligand-to-metal ratios used in the complexation reaction. Two different kinds of luminescent dinuclear complex structures and a kind of tetranuclear complex structure were revealed by X-ray single-crystal analyses and were further investigated for their photophysical properties. The emission maxima of these complexes are in the blue to yellow region of the visible spectrum for the dinuclear complexes and in the yellow to orange region for the tetranuclear complexes. Further investigations using density functional theory (DFT) show that the highest occupied molecular orbital (HOMO) is located mainly on the metal halide cores, while the lowest unoccupied molecular orbital (LUMO) resides mostly in the ligand sphere of the complexes. The emission properties were further examined in different environments such as neat powders, neat films, PMMA matrices, or dichloromethane solutions, revealing the high potential of these complexes for their application in organic light-emitting diodes. Especially complexes with 1,2,4-triazole moieties feature emission maxima in the blue region of the visible spectrum and quantum yields up to 95% together with short decay times of about 1–4 μs and are therefore promising candidates for blue-emitting materials in OLEDs

Dual-Stimuli-Responsive Microparticles

The need for smart materials in the area of biotechnology has fueled the development of numerous stimuli-responsive polymers. Many of these polymers are responsive to pH, light, temperature, or oxidative stress, and yet very few are responsive toward multiple stimuli. Here we report on the synthesis of a novel dual-stimuli-responsive poly­(ethylene glycol)-based polymer capable of changing its hydrophilic properties upon treatment with UV light (exogenous stimulus) and markers of oxidative stress (endogenous stimulus). From this polymer, smart microparticles and fibers were fabricated and their responses to either stimulus separately and in conjunction were examined. Comparison of the degradation kinetics demonstrated that the polymer became water-soluble only after both oxidation and irradiation with UV light, which resulted in selective degradation of the corresponding particles. Furthermore, in vitro experiments demonstrated successful uptake of these particles by Raw 264.7 cells. Such dual-stimuli-responsive particles could have potential applications in drug delivery, imaging, and tissue engineering

Copper(I) Complexes Based on Five-Membered P^∧N Heterocycles: Structural Diversity Linked to Exciting Luminescence Properties

Bridging P^∧N ligands bearing five-membered heterocyclic moieties such as tetrazoles, 1,2,4-triazoles, oxadiazoles, thiadiazoles, and oxazoles have been investigated regarding their complexation behavior with copper­(I) iodide as metal salts. Different complex structures were found, depending either on the ligand itself or on the ligand-to-metal ratios used in the complexation reaction. Two different kinds of luminescent dinuclear complex structures and a kind of tetranuclear complex structure were revealed by X-ray single-crystal analyses and were further investigated for their photophysical properties. The emission maxima of these complexes are in the blue to yellow region of the visible spectrum for the dinuclear complexes and in the yellow to orange region for the tetranuclear complexes. Further investigations using density functional theory (DFT) show that the highest occupied molecular orbital (HOMO) is located mainly on the metal halide cores, while the lowest unoccupied molecular orbital (LUMO) resides mostly in the ligand sphere of the complexes. The emission properties were further examined in different environments such as neat powders, neat films, PMMA matrices, or dichloromethane solutions, revealing the high potential of these complexes for their application in organic light-emitting diodes. Especially complexes with 1,2,4-triazole moieties feature emission maxima in the blue region of the visible spectrum and quantum yields up to 95% together with short decay times of about 1–4 μs and are therefore promising candidates for blue-emitting materials in OLEDs

Antibacterial Activity of Sulfamethoxazole Transformation Products (TPs): General Relevance for Sulfonamide TPs Modified at the <i>para</i> Position

Sulfonamide antibiotics undergo transformation in the aquatic environment through biodegradation, photolysis, or hydrolysis. In this study, the residual antibacterial activity of 11 transformation products (TPs) of sulfamethoxazole (SMX) was investigated with regard to their <i>in vitro</i> growth and luminescence inhibition on Vibrio fischeri (30 min and 24 h exposure). Two transformation products, 4-hydroxy-SMX and <i>N</i>⁴-hydroxy-acetyl-SMX, were synthesized in-house and confirmed by nuclear magnetic resonance and high-resolution mass spectrometry. Results of individual compound experiments showed that TPs modified at the <i>para</i> amino group still exhibit clear antibacterial effects, whereas TPs resulting from breakdown of the SMX structure lost this mechanism of action. 4-NO₂- and 4-OH-SMX were found to inhibit growth to a clearly greater extent than the parent compound, SMX. In contrast, the <i>N</i>⁴-acetyl- and <i>N</i>⁴-hydroxy-acetyl-derivatives retain less than 10 and 5% of the effect of SMX on growth and luminescence inhibition, respectively. The effect of a mixture of <i>para</i>-modified TPs was observed to be additive. Considering the homologous series of sulfa drugs widely prescribed and their common mechanism of action, the potential environmental impact must consider the total amount of sulfonamide antibiotics and their derivative TPs, which might end up in a water body. Extrapolating the results obtained here for the <i>para </i>TPs of SMX to other sulfa drugs and determining the persistence and occurrence of these compounds in the aquatic environment is required for improved risk assessment

Structure Revision of Plakotenin Based on Computational Investigation of Transition States and Spectroscopic Properties

We show that the previously [<i>Tetrahedron Lett.</i> <b>1992</b>, <i>33</i>, 2579] proposed structure of natural plakotenin must be revised. Recently, the total synthesis of plakotenin was achieved via an intramolecular Diels–Alder reaction from a (<i>E,E,Z,E</i>)-tetraene as linear precursor. Using density functional theory, the computation of the four possible transition states for this reaction shows that the previously proposed structure could only have been formed via an energetically high-lying transition state, which is very unlikely. Instead, we suggest that the structure of plakotenin corresponds to the product formed via the lowest transition state. A comparison of experimental and theoretical optical rotation, circular dichroism, and two-dimensional nuclear Overhauser enhancement spectra conclusively proves that the structure of plakotenin is the one that is suggested by the transition state computations. Moreover, the simulation of the nuclear Overhauser enhancement spectra suggests that it is most likely that the misassignment of the ¹H chemical shifts of two methyl groups has led to the wrong structure prediction in the 1992 work. The previously proposed structure of <i>iso</i>-plakotenin remains unaffected by our structure revision, but the structures of <i>homo</i>- and <i>nor</i>-plakotenin must also be revised. The present work shows how the total synthesis of a natural product, together with the theoretical determination of the barrier heights of the reactions involved, can be of great help to assign its structure. It appears that intramolecular Diels–Alder reactions can be modeled accurately by today’s first-principles methods of quantum chemistry