HOMO Stabilisation in π‐Extended Dibenzotetrathiafulvalene Derivatives for Their Application in Organic Field‐Effect Transistors

Three new organic semiconductors, in which either two methoxy units are directly linked to a dibenzotetrathiafulvalene (DB‐TTF) central core and a 2,1,3‐chalcogendiazole is fused on the one side, or four methoxy groups are linked to the DB‐TTF, have been synthesised as active materials for organic field‐effect transistors (OFETs). Their electrochemical behaviour, electronic absorption and fluorescence emission as well as photoinduced intramolecular charge transfer were studied. The electron‐withdrawing 2,1,3‐chalcogendiazole unit significantly affects the electronic properties of these semiconductors, lowering both the HOMO and LUMO energy levels and hence increasing the stability of the semiconducting material. The solution‐processed single‐crystal transistors exhibit high performance with a hole mobility up to 0.04 cm² V^?1 s^?1 as well as good ambient stability.     

Access to the Aeruginosin Serine Protease Inhibitors through the Nucleophilic Opening of an Oxabicyclo[2.2.1]heptane: Total Synthesis of Microcin SF608

Serine proteases play key roles in many biological processes and are associated with several human diseases such as thrombosis or cancer. During the search for selective inhibitors of serine proteases, a family of linear peptides named the aeruginosins was discovered in marine cyanobacteria. We herein report an entry route into the synthetically challenging core fragment of these natural products. Starting from the common oxabicyclic building block 11 , we accessed the octahydroindole core of the aeruginosins, exemplified by the total synthesis of microcin SF608 ( 2 ). Key to the synthetic strategy is a highly efficient nucleophilic opening of an oxabicyclo[2.2.1]heptane producing the hydroindole motif of microcin SF608. Moreover, during the synthetic efforts we have observed an unusual regioselective epoxide reduction. Detailed experimental studies of this reaction led us to propose a mechanistic rationale involving intramolecular hydrogen atom delivery by a carbamate NH group to control the regioselectivity of the homolytic epoxide cleavage.     

Lead Structures for New Antibacterials: Stereocontrolled Synthesis of a Bioactive Muraymycin Analogue

Naturally occurring muraymycin nucleoside antibiotics represent a promising class of novel antibacterial agents. The structural complexity suggests the investigation of simplified analogues as potential lead structures, which can then be further optimized towards highly potent antimicrobials. Herein we report studies on muraymycin‐derived potential lead structures lacking an aminoribose motif found in most naturally occurring muraymycins. We have identified a 5′‐defunctionalized motif to be ideal in terms of stability and chemical accessibility and have synthesized a full‐length muraymycin analogue based on this structure using a novel fully stereocontrolled route. The obtained 5′‐deoxy analogue of the natural product muraymycin C4 showed good inhibitory properties towards the bacterial target protein MraY, sufficient pharmacokinetic stability and no cytotoxicity against human cells, thus making it a promising lead for antibacterial drug development.     

Magnetically Encoded Luminescent Composite Nanoparticles through Layer‐by‐Layer Self‐Assembly

Sensitive and rapid detection of multiple analytes and the collection of components from complex samples are important in fields ranging from bioassays/chemical assays, clinical diagnosis, to environmental monitoring. A convenient strategy for creating magnetically encoded luminescent CdTe@SiO₂@n Fe₃O₄ composite nanoparticles, by using a layer‐by‐layer self‐assembly approach based on electrostatic interactions, is described. Silica‐coated CdTe quantum dots (CdTe@SiO₂) serve as core templates for the deposition of alternating layers of Fe₃O₄ magnetic nanoparticles and poly(dimethyldiallyl ammonium chloride), to construct CdTe@SiO₂@n Fe₃O₄ (n=1, 2, 3, …?) composite nanoparticles with a defined number (n) of Fe₃O₄ layers. Composite nanoparticles were characterized by zeta‐potential analysis, fluorescence spectroscopy, vibrating sample magnetometry, and transmission electron microscopy, which showed that the CdTe@SiO₂@n Fe₃O₄ composite nanoparticles exhibited excellent luminescence properties coupled with well‐defined magnetic responses. To demonstrate the utility of these magnetically encoded nanoparticles for near‐simultaneous detection and separation of multiple components from complex samples, three different fluorescently labeled IgG proteins, as model targets, were identified and collected from a mixture by using the CdTe@SiO₂@n Fe₃O₄ nanoparticles.     

A Deadly Organometallic Luminescent Probe: Anticancer Activity of a ReI Bisquinoline Complex

The photophysical properties of [Re(CO)₃(L ‐N₃)]Br (L ‐N₃=2‐azido‐N,N‐bis[(quinolin‐2‐yl)methyl]ethanamine), which could not be localized in cancer cells by fluorescence microscopy, have been revisited in order to evaluate its use as a luminescent probe in a biological environment. The Re^I complex displays concentration‐dependent residual fluorescence besides the expected phosphorescence, and the nature of the emitting excited states have been evaluated by DFT and time‐dependent (TD) DFT methods. The results show that fluorescence occurs from a ¹LC/MLCT state, whereas phosphorescence mainly stems from a ³LC state, in contrast to previous assignments. We found that our luminescent probe, [Re(CO)₃(L ‐N₃)]Br, exhibits an interesting cytotoxic activity in the low micromolar range in various cancer cell lines. Several biochemical assays were performed to unveil the cytotoxic mechanism of the organometallic Re^I bisquinoline complex. [Re(CO)₃(L ‐N₃)]Br was found to be stable in human plasma indicating that [Re(CO)₃(L ‐N₃)]Br itself and not a decomposition product is responsible for the observed cytotoxicity. Addition of [Re(CO)₃(L ‐N₃)]Br to MCF‐7 breast cancer cells grown on a biosensor chip micro‐bioreactor immediately led to reduced cellular respiration and increased glycolysis, indicating a large shift in cellular metabolism and inhibition of mitochondrial activity. Further analysis of respiration of isolated mitochondria clearly showed that mitochondrial respiratory activity was a direct target of [Re(CO)₃(L ‐N₃)]Br and involved two modes of action, namely increased respiration at lower concentrations, potentially through increased proton transport through the inner mitochondrial membrane, and efficient blocking of respiration at higher concentrations. Thus, we believe that the direct targeting of mitochondria in cells by [Re(CO)₃(L ‐N₃)]Br is responsible for the anticancer activity.     

Tuning Thiophene with Phosphorus: Synthesis and Electronic Properties of Benzobisthiaphospholes

1,4‐Dimercapto‐2,5‐diphosphinobenzene and 3,6‐bis(hexyloxy)‐1,4‐dimercapto‐2,5‐diphosphinobenzene were synthesized and combined with various acid chlorides to obtain a series of benzobisthiaphospholes. Electrochemical and photophysical properties of the substituted benzobisthiaphospholes have been evaluated, and the observed reductions are more facile than the related benzothiaphospholes and 2,6‐diphenylbenzobisthiazole. A benzobisthiaphosphole with C₆H₄‐p‐CN substituents was reduced at E_1/2=?1.08 V (vs. saturated calomel electrode (SCE)). X‐ray diffraction data for several of these phosphorus heterocycles has been obtained, and DFT calculations at the B3LYP level have been performed.     

Hydroxymethylated Phyllobilins: A Puzzling New Feature of the Dioxobilin Branch of Chlorophyll Breakdown

Colorless nonfluorescent chlorophyll (Chl) catabolites (NCCs) are formyloxobilin‐type phyllobilins, which are considered the typical products of Chl breakdown in senescent leaves. However, in degreened leaves of some plants, dioxobilin‐type Chl catabolites (DCCs) predominate, which lack the formyl group of the NCCs, and which arise from Chl catabolites by oxidative removal of the formyl group by a P450 enzyme. Here a structural investigation of the DCCs in the methylesterase16 mutant of Arabidopsis thaliana is reported. Eight new DCCs were identified and characterized structurally. Strikingly, three of these DCCs carry stereospecifically added hydroxymethyl groups, and represent bilin‐type linear tetrapyrroles with an unprecedented modification. Indeed, DCCs show a remarkable structural parallel, otherwise, to the bilins from heme breakdown.     

Functionalized Membranes for Photocatalytic Hydrogen Production

Functionalized vesicles for photocatalytic hydrogen production in water have been prepared by co‐embedding of amphiphilic photosensitizers and a hydrogen‐evolving catalyst in phospholipid membranes. The self‐assembly allows a simple two‐dimensional arrangement of the multicomponent system with close spatial proximity, which gave turnover numbers up to 165 for the incorporated amphiphilic cobaloxime water reduction catalyst 3 b under optimized conditions in purely aqueous solution. Superior photocatalytic activity in fluid membranes indicates that mobility and dynamic reorganization of catalytic subunits in the membrane promote the visible‐light‐driven hydrogen production. The functionalized membranes represent nanostructured assemblies for hydrogen production in aqueous solution mimicking natural photosynthesis.     

New Polydentate Trimethylsilyl Chalcogenide Reagents for the Assembly of Polyferrocenyl Architectures

A series of polychalcogenotrimethylsilane complexes Ar(CH₂ESiMe₃)_n, (Ar=aryl; E=S, Se; n=2, 3, and 4) can be prepared from the corresponding polyorganobromide and M[ESiMe₃] (M=Na, Li). These represent the first examples of the incorporation of such a large number of reactive ?ESiMe₃ moieties onto an organic molecular framework. They are shown to be convenient reagents for the preparation of the polyferrocenylseleno‐ and thioesters from ferrocenoyl chloride. The synthesis, structures, and spectroscopic properties of the new silyl chalcogen complexes 1,4‐(Me₃SiECH₂)₂(C₆Me₄) (E=S, 1 ; E=Se, 2 ), 1,3,5‐(Me₃SiECH₂)₃(C₆Me₃) (E=S, 3 ; E=Se, 4 ) and 1,2,4,5‐(Me₃SiECH₂)₄(C₆H₂) (E=S, 5 ; E=Se, 6 ) and the polyferrocenyl chalcogenoesters [1,4‐{FcC(O)ECH₂}₂(C₆Me₄)] (E=S, 7 ; E=Se, 8 ), [1,3,5‐{FcC(O)ECH₂}₃(C₆Me₃)] (E=S, 9 ; E=Se, 10 ) and [1,2,4,5‐{FcC(O)ECH₂}₄(C₆H₂)] (E=S, 11 illustrated; E=Se, 12 ) are reported. The new polysilylated reagents and polyferrocenyl chalcogenoesters have been characterized by multinuclear NMR spectroscopy (¹H, ¹³C, ⁷⁷Se), electrospray ionization mass spectrometry and, for complexes 1 , 2 , 3 , 4 , 7 , 8 , and 11 , single‐crystal X‐ray diffraction. The cyclic voltammograms of complexes 7 – 11 are presented.     

Polar Red‐Emitting Rhodamine Dyes with Reactive Groups: Synthesis,Photophysical Properties,and Two‐Color STED Nanoscopy Applications

The synthesis, reactivity, and photophysical properties of new rhodamines with intense red fluorescence, two polar residues (hydroxyls, primary phosphates, or sulfonic acid groups), and improved hydrolytic stability of the amino‐reactive sites (NHS esters or mixed N‐succinimidyl carbonates) are reported. All fluorophores contain an N‐alkyl‐1,2‐dihydro‐2,2,4‐trimethylquinoline fragment, and most of them bear a fully substituted tetrafluoro phenyl ring with a secondary carboxamide group. The absorption and emission maxima in water are in the range of 635–639 and 655–659 nm, respectively. A vastly simplified approach to red‐emitting rhodamines with two phosphate groups that are compatible with diverse functional linkers was developed. As an example, a phosphorylated dye with an azide residue was prepared and was used in a click reaction with a strained alkyne bearing an N‐hydroxysuccinimid (NHS) ester group. This method bypasses the undesired activation of phosphate groups, and gives an amphiphilic amino‐reactive dye, the solubility and distribution of which between aqueous and organic phases can be controlled by varying the pH. The presence of two hydroxyl groups and a phenyl ring with two carboxyl residues in the dyes with another substitution pattern is sufficient for providing the hydrophilic properties. Selective formation of a mono‐N‐hydroxysuccinimidyl ester from 5‐carboxy isomer of this rhodamine is reported. The fluorescence quantum yields varied from 58 to 92 % for free fluorophores, and amounted to 18–64 % for antibody conjugates in aqueous buffers. The brightness and photostability of these fluorophores facilitated two‐color stimulated emission depletion (STED) fluorescence nanoscopy of biological samples with high contrast and minimal background. Selecting a pair of fluorophores with absorption/emission bands at 579/609 and 635/655 nm enabled two‐color channels with low cross‐talk and negligible background at approximately 40 nm resolution.