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Singlet oxygen is a powerful oxidant used in various applications, such as organic synthesis, medicine, and environmental remediation. Organic and inorganic photosensitizers are commonly used to generate this reactive species through energy transfer with the triplet ground state of oxygen. We describe here a series of novel benzophenazine derivatives as a promising class of photosensitizers for singlet oxygen photosensitization. In this study, we investigated the structure‐activity relationship of these benzophenazine derivatives. Akin to a molecular compass, the southern fragment was first functionalized with either aromatic tertiary amines, alkyl tertiary amines, aromatic sulfur groups, alkyl sulfur groups, or cyclic ethers. Enhanced photophysical properties (in terms of triplet excited‐state lifetime, absorption wavelength, triplet state energy, and O2 quenching capabilities) were obtained with cyclic ether and sulfur groups. Conversely, the presence of an amine moiety was detrimental to the photocatalysts. The western and northern fragments were also investigated and slightly undesirable to negligible changes in photophysical properties were observed. The most promising candidate was then immobilized on silica nanoparticles and its photoactivity was evaluated in the citronellol photooxidation reaction. A high NMR yield of 97 % in desired product was obtained, with only a slight decrease over several recycling runs (85 % in the fourth run). These results provide insights into the design of efficient photosensitizers for singlet oxygen generation and the development of heterogeneous systems. [ABSTRACT FROM AUTHOR]

The restriction of plant‐symbiont dinitrogen fixation by an insect semiochemical had not been previously described. Here we report on a glycosylated triketide δ‐lactone from Nephrotoma cornicina crane flies, cornicinine, that causes chlorosis in the floating‐fern symbioses from the genus Azolla. Only the glycosylated trans‐A form of chemically synthesized cornicinine was active: 500 nM cornicinine in the growth medium turned all cyanobacterial filaments from Nostoc azollae inside the host leaf‐cavities into akinetes typically secreting CTB‐bacteriocins. Cornicinine further inhibited akinete germination in Azolla sporelings, precluding re‐establishment of the symbiosis during sexual reproduction. It did not impact development of the plant Arabidopsis thaliana or several free‐living cyanobacteria from the genera Anabaena or Nostoc but affected the fern host without cyanobiont. Fern‐host mRNA sequencing from isolated leaf cavities confirmed high NH4‐assimilation and proanthocyanidin biosynthesis in this trichome‐rich tissue. After cornicinine treatment, it revealed activation of Cullin‐RING ubiquitin‐ligase‐pathways, known to mediate metabolite signaling and plant elicitation consistent with the chlorosis phenotype, and increased JA‐oxidase, sulfate transport and exosome formation. The work begins to uncover molecular mechanisms of cyanobiont differentiation in a seed‐free plant symbiosis important for wetland ecology or circular crop‐production today, that once caused massive CO2 draw‐down during the Eocene geological past. Summary Statement: The glycosylated triketide δ‐lactone cornicinine from crane flies elicited and maintained cyanobiont akinete differentiation in mosquito fern symbioses sharing the wetland habitat; it revealed processes of cell‐differentiation in ecologically significant N2‐fixing symbioses with cyanobacteria. [ABSTRACT FROM AUTHOR]

An efficient and unprecedented cross‐coupling between acylzirconocenes, readily available starting materials conveniently prepared by hydrozirconation of alkenes and a subsequent carbonylation with carbon monoxide, and diaryliodonium tetrafluoroborates is reported. This procedure enables the synthesis of a broad variety of alkyl‐aryl‐ketones upon simple catalysis with copper cyanide without the need of additional ligands and only requires a low pressure of carbon monoxide generated in situ, in a two‐chamber reactor, from N‐formylsaccharin. [ABSTRACT FROM AUTHOR]

Earth‐abundant photosensitizers are highly sought after for light‐mediated applications, such as photoredox catalysis, depollution and energy conversion schemes. Homoleptic and heteroleptic copper(I) complexes are promising candidates in this field, as copper is abundant and the corresponding complexes are easily obtained in smooth conditions. However, some heteroleptic copper(I) complexes suffer from low (photo)stability that leads to the gradual formation of the corresponding homoleptic complex. Such degradation pathways are detrimental, especially when recyclability is desired. This study reports a novel approach for the heterogenization of homoleptic and heteroleptic Cu complexes on silica nanoparticles. In both cases, the photophysical properties upon surface immobilization were only slightly affected. Excited‐state quenching with aryl diazonium derivatives occurred efficiently (108–1010 M−1 s−1) with heterogeneous and homogeneous photosensitizers. Moderate but almost identical yields were obtained for the α‐arylation of enol acetate using the homoleptic complex in homogeneous or heterogeneous conditions. Importantly, the silica‐supported photocatalysts were recycled with moderate loss in photoactivity over multiple experiments. Transient absorption spectroscopy confirmed that excited‐state electron transfer occurred from the homogeneous and heterogeneous homoleptic copper(I) complexes to aryl diazonium derivatives, generating the corresponding copper(II) center that persisted for several hundreds of microseconds, compatible with photoredox catalysis applications. [ABSTRACT FROM AUTHOR]

A modified total synthesis of (S)-goniothalamin is described for an advanced course in organic chemistry. This experiment gives students an opportunity to handle organometallic reagents and perform an enzymatic kinetic resolution and a metathesis reaction, all in the same synthesis. Furthermore, students learn flame-drying techniques for the manipulation of air-sensitive materials and high-performance liquid chromatography handling and analysis, thus strengthening their experimental knowledge.

A statistical approach was successfully applied to optimize the acylation of l‐menthol 1 in the presence of natural kaolin as an eco‐compatible catalyst. The influence of the main variation of the operating parameters, namely solvent volume, amount of the acyl donor, temperature and the catalytic rate of kaolin, was studied. A full factorial design (FFD) was used to search for the optimum of each parameter affecting the evolution of l‐menthol 1 acylation. A quadratic polynomial regression model was applied to analyse the experimental data with a p‐confidence level <.05 (95%). Statistical analysis of the data confirmed that temperature (T), acyl donor/acceptor ratio (Qa), kaolin mass (Qc) and solvent volume (V) were the significant factors affecting the l‐menthol catalytic acylation process. The determination coefficient of the adopted model was in the order of 98%. A set of optimal reaction conditions was established, and experimental tests were performed to validate the optimal conditions; the threshold of 100% was reached. Monitoring the kinetic profile of the reaction by gas chromatography (GC) showed complete conversion after 30 min of reaction. An upgrade of this developed environmentally benign process was applied to some monoterpenic alcohols, and the corresponding acetates were yielding at 45%–90%. [ABSTRACT FROM AUTHOR]

In this work, we developed a one-pot, copper-catalyzed aminodifluoroalkylation of enylaniline derivatives. This approach allows the catalytic construction of a broad range of pyrrolidines and piperidines substituted with a gem -difluoro moiety. [ABSTRACT FROM AUTHOR]

Simple Summary: To identify inhibitors of mitochondrial respiration as potential anticancer drugs is not an easy matter since cancer cells cultured as monolayers may escape by shifting their metabolic preference toward the use of glycolysis. Here we propose to capitalize on this apparent weakness to exploit the associated increase in L-lactate release as a primary screening assay to identify and optimize the development of inhibitors of mitochondrial oxidative phosphorylation. As a secondary assay, we used a protocol based on O2 consumption rate in permeabilized cancer cells to get further insights on a possible direct or indirect inhibition of mitochondrial electron transport chain. Finally, 3D tumor spheroids helped us to further select drug candidates endowed with the capacity to exert growth inhibitory effects in tumor-mimicking conditions but also to act as potent radiosensitizers by promoting reoxygenation. Cancer cells may stimulate glycolytic flux when O2 becomes insufficient. Increase in L-lactate release therefore appears as an escape mechanism to drugs targeting mitochondrial respiration but also represents a response that may be exploited to screen for compounds blocking either mitochondrial carriers of oxidizable substrates or the electron transport chain. Here, we developed a screening procedure based on the capacity of cancer cells to release L-lactate to gain insights on the development of mitochondrial complex I inhibitors. For this purpose, we synthesized derivatives of carboxyamidotriazole, a compound previously described as a potential OXPHOS inhibitor. Two series of derivatives were generated by cycloaddition between benzylazide and either cyanoacetamides or alkynes. A primary assay measuring L-lactate release as a compensatory mechanism upon OXPHOS inhibition led us to identify 15 hits among 28 derivatives. A secondary assay measuring O2 consumption in permeabilized cancer cells confirmed that 12 compounds among the hits exhibited reversible complex I inhibitory activity. Anticancer effects of a short list of 5 compounds identified to induce more L-lactate release than reference compound were then evaluated on cancer cells and tumor-mimicking 3D spheroids. Human and mouse cancer cell monolayers exhibiting high level of respiration in basal conditions were up to 3-fold more sensitive than less oxidative cancer cells. 3D tumor spheroids further revealed potency differences between selected compounds in terms of cytotoxicity but also radiosensitizing activity resulting from local reoxygenation. In conclusion, this study documents the feasibility to efficiently screen in 96-well plate format for mitochondrial complex I inhibitors based on the capacity of drug candidates to induce L-lactate release. [ABSTRACT FROM AUTHOR]

The highly chemoselective protection of various aldehydes by natural kaolin as a catalyst was reported. This clay was characterised by XRD, FTIR, BET and SEM techniques. The acetalization reaction was executed in ethanol as solvant and produces the corresponding acetals with moderate to excellent yields and high chemoselectivity (0 %

Several new ferrocene derivatives bearing two donor-acceptor systems are reported in which the ferrocene unit has acted both as a donor group and as a rotating spacer. These ferrocene sensors have allowed the naked-eye selective colorimetric detection of copper[II] cation and of benzoate, acetate, or cyanide anions, all anions of special toxicological and biological relevance.

An efficient enantioselective synthesis of a set of (R)‐phenylalkylesters and their analogues amides via enzymatic acylation of 1‐phenylethanol (rac‐1) and 1‐phenylethanamine (rac‐2) using carboxylic acids with different chain‐lengths as green acyl donor is reported. Three lipases are used: Candida antarctica B immobilized on acrylic resin (CAL‐B) and two free lipases: Pseudomonas cepacia (PCL) and Candida rugosa (CRL). The CAL‐B shows an excellent selectivity during the acylation of rac‐1 without restriction due to the acyl carbon chain‐length, the (R)‐ esters (1 a–1 f) were obtained enantiopures (ee up to 99 %). For the first time, the PCL catalyzed O‐acylation allows smoothly to (R)‐(1 d–1 f) with high selectivity (E⋙200) is described. The conversions increase with the length of the carbon‐chain of the acyl donor (28.7 %≤C≤40 %). The CRL shows less selective and provided the (R) (1 b–1 e) with 77 %≤eep≤86.4 %. Due to its high thermostability, the CAL‐B is used for the N‐acylation of rac‐2 and provides access to enantioenriched (R)‐fatty amides (2 d–2 f) (60.7 %≤eep≤74.4 %) and the remained (S)‐2 with ees>91 %. [ABSTRACT FROM AUTHOR]

Research was conducted to examine a straightforward asymmetric synthesis of enantiopure 1,2-disubstituted ferrocenes. The strategy is based on a chiral ferrocenyl sulfoxide and consists of a three-step process. The first is the preparation of (r)- or (S)-ferrocenyl p-tolyl sulfoxide from ferrocene. Second is the diastereoselective ortho-functionalization of sulfoxide 2 to sulfoxide 3. Third is introduction of the R2 group. Results show excellent yields for the transformation of 3 -> 4.

This report describes the synthesis of a carbon nanotube‐bound dendrimer and three carbon nanotube‐bound monometallic complexes and their use as catalysts. The polyamidoamine third generation dendrimer used here incorporates pyrazole‐triazole moieties suitable for ligating iridium(III) centres. The monometallic complexes use the same pyrazole‐triazole ligands coordinated to an iridium(III) centre. All catalysts were characterized using ICP‐AES and XPS to evaluate their metal loadings on the carbon surface with significantly higher relative weight percentage of iridium determined for the denrimeric species. The catalytic activity and practicality of the formed catalysts were tested using two different intramolecular hydroamination reactions. [ABSTRACT FROM AUTHOR]

The use of chiral catalysts in asymmetric Diels-Alder (DA) reactions is described. DA, a standard method for six-membered ring formation, is suited to the building of stereogenic centers due to its natural cyclic transition state involving suprafacial interaction. But the process becomes practical only with the use ofchiral Lewis acids (LA) to catalyze the DA reaction under mild conditions, allowing very high (90-95%) diastereomeric and enantiomeric excesses. Chiral LAs based on aluminum, titanium, boron and transition metal complexes, as well as non-LA catalysts, are discussed.