Israel Journal of Chemistry最新文献

Nickel-catalyzed cross-electrophile coupling (XEC) is an efficient method to form carbon-carbon bonds and has become an important tool for building complex molecules. While XEC has most often used stoichiometric metal reductants, these transformations can also be driven electrochemically. Electrochemical XEC (eXEC) is attractive because it can increase the greenness of XEC and this potential has resulted in numerous advances in recent years. The focus of this review is on electrochemical, Ni-catalyzed carbon-carbon bond forming reactions reported since 2010 and is categorized by the type of anodic half reaction: sacrificial anode, sacrificial reductant, and convergent paired electrolysis. The key developments are highlighted and the need for more scalable options is discussed.

An “OFF/ON” electric current switching protocol was developed as a new strategy for one-pot organic synthesis. Suzuki-Miyaura coupling of 2-bromopyridines with arylboronic acids in an electrochemical cell was performed without applying an electric current, and subsequently, the Pd-catalyzed electrochemical C−H bromination was conducted using the already-present Pd catalyst to obtain 2-(2-bromoaryl)pyridines as products. The one-pot synthesis of bromoarenes can also be achieved without adding an external Br source in the second step. Furthermore, an OFF/ON/OFF two-times switching protocol also realized the formation of an N-containing teraryl derivative.

A novel metal- and oxidant-free electrooxidative selenylamination of o-aminophenacetylenes with diselenides for achieving 3-selenylindoles has been developed with moderate to excellent yield. The reaction proceeded smoothly with a broad substrate scope and highly functional group tolerance. The synthetic practicality of this innovative approach was demonstrated by its easy scalability. Moreover, mechanistic studies revealed that an in-situ generated selenium cation might be the key intermediate for the electrochemical selenocyclization process.

Infections with multidrug-resistant Gram-negative bacteria constitute a silent pandemic threat that is increasing globally. A major technical and scientific hurdle hampering the development of efficient antibiotics against Gram-negative species is the low permeability of their outer membrane that prevents the entry of most small molecules into the cells. This can be overcome by targeting active iron transport systems of the pathogens in a Trojan-Horse strategy that makes use of drug-loaded artificial siderophores. While we utilized catechols as iron-binding motifs in previous work, this study reports the design, synthesis and characterization of siderophores with a DOTAM scaffold that was substituted with three hydroxamate arms allowing for a hexacoordination of iron. Their iron-chelating capabilities were shown colorimetrically, and the ability of compound 1 to deliver iron into Escherichia coli in a chelation-specific manner was proven by a growth recovery assay. A covalent siderophore-ciprofloxacin conjugate exerted antibiotic effects against E. coli, albeit it was less potent than the free drug. The study qualifies artificial DOTAM siderophores with hydroxamate binders as scaffolds for bacterial Trojan Horses. This contribution for honoring my mentor Helmut Schwarz echoes two motifs of my work with him: Hydroxylamin, the topic of my first paper ever, and the fascinating properties of iron ions, studied in the gas phase during my Ph.D. Thesis, became a core subject of our current chemical biology research on antiinfectives.

The functional roles of structured RNAs in the regulation of biological processes, and hence RNA's potential as an effective therapeutic target, have only recently been appreciated. Robust and high-throughput methods that identify potent RNA ligands are critical to the development of chemical probes and therapeutics. DNA-encoded libraries (DEL) technology has emerged as a powerful tool for protein ligand discovery, and its ability to generate large, custom-tailored, and novel chemical space offers unprecedented opportunities to discover the rules of RNA ligand design. In this review, we discuss the basic principles of DEL selection, current progress on the application of DEL to RNA targets, and the outlook of targeting RNA by DEL.

Self-folding cavitands represent the quintessential form of bioinspired synthetic receptors, featuring deep hydrophobic cavities that engage in host-guest chemistry reminiscent of that operating in biomolecules. Although remarkable proof-of-concept applications have been reported, the narrow and rigid spaces of the legacy resorcin[4]arene derived hosts constitute a liability towards the development of specific applications in catalysis, sensing or sequestration. While notable efforts to expand the size of the cavities have been reported, the development of confined spaces reproducing the highly adaptable nature of biological receptors is a largely unaddressed issue. This review summarizes the development of a new family of calix[5]arene derived self-folding cavitands displaying enhanced induced fit and conformational selection phenomena. Our approach capitalizes on hydrogen bonding preorganization rather than the covalent restriction approaches customary of conventional supramolecular chemistry.

Quantum chemical calculations have been carried out at the BP86/def2-SVP level on Ge₈(Sit-butyl₂methyl)₆ (1) and the bonding situation has been analyzed with a variety of methods. The calculated equilibrium geometry of 1 is in good agreement with the reported x-ray structure analysis. The D3 correction for dispersion interactions as a sum of pairwise attractions leads to an overestimate of the effect of dispersion forces. Calculations at BP86-D3(BJ)/def2-SVP give shorter bonds for Ge(I)−Ge(I) than for Ge(0)−Ge(I), which is in contrast to the experimental values and the BP86/def2-SVP results. The NBO analysis suggests that the best Lewis structure of 1 has lone-pair orbitals at the Ge(0) atoms with occupation numbers of 1.70 e. A lone-pair character at Ge(0) albeit with less weight is also suggested by the shape of the HOMO, which is an antibonding orbital between the Ge(0) atoms with small contributions from the Ge(I) atoms. The LUMO of 1 is the corresponding bonding combination of the Ge(0) AOs, which can be explained with the reluctance of the heavier main-group atoms to s/p hybridization of the valence orbitals. The calculated bond order values suggest significant direct Ge(0)−Ge(0) interactions. This is supported by the shape of the HOMO and by the results of EDA-NOCV calculations. The deformation densities and the orbitals associated with the pairwise orbital interaction show that there is a direct charge flow between the Ge(0) atoms of the two fragments, but it is not completely separated from the Ge(0)−Ge(I) and Ge(I)−Ge(I) bond formation. The QTAIM calculations suggest that 1 has a cubic structure with a cage critical point but not a bond critical point for the Ge(0)−Ge(0) interactions. The dispersion interactions of the large substituents in 1 have a significant influence on the stability of the compound.

Richard Lerner was a visionary polymath of the 20^th century; a medical doctor, chemist, immunologist, inventor, and founder of new scientific fields. As a tribute to his life and scientific achievements, we discuss his connection with Oxford University and the Glycobiology Institute and we discuss our research data on the host glycoprotein folding pathway and how its inhibition can lead to broad spectrum antiviral drugs. This host targeting approach for developing antiviral therapies has the advantage of being effective against many viruses, therefore can be used to prevent new epidemics to become pandemics.

The reactivity of a carbon-centered σ,σ,σ,σ-type singlet tetraradical containing two meta-benzyne moieties, the 2,4,5,7-tetradehydroquinolinium cation, was examined in the gas phase toward dimethyl disulfide, cyclohexane and allyl iodide. The major reactions were thiomethyl radical abstraction, H atom abstraction and allyl radical abstraction, respectively. The reactivity of this tetraradical was found to be greater than that of the relevant meta-benzyne biradicals. The reactivity of individual meta-benzynes has been found previously to be controlled by their (calculated) distortion energies (ΔE_2.30) and singlet-triplet spittings (ΔE_S-T) as well as their electron affinities (EA_2.30) at the TS geometry for hydrogen atom abstraction reactions. The addition of another meta-benzyne moiety to a meta-benzyne to generate the above tetraradical does not change EA_2.30 and only slightly lowers ΔE_S-T of both meta-benzyne moieties. However, ΔE_2.30 is significantly decreased for both meta-benzyne moieties, which explains the higher reactivity of the tetraradical. A similar finding was made previously for an isomeric tetraradical, the 2,4,6,8-tetradehydroquinolinium cation, that also contains two meta-benzyne moieties. The decrease in ΔE_2.30 is rationalized by a stabilizing coupling between one radical site in each meta-benzyne moiety for both tetraradicals. Interestingly, the more reactive meta-benzyne moiety in the two tetraradicals was found to be different: that in the pyridine ring (2,4−) is more reactive for the 2,4,5,7-tetraradical while that in the benzene ring (6,8−) is more reactive for the 2,4,6,8-tetraradical. This difference is rationalized by the uniquely small ΔE_2.30 value for the 6,8-moiety in the 2,4,6,8-tetraradical, which makes this moiety (and this tetraradical) unusually reactive. On the other hand, the ΔE_2.30 values for the meta-benzyne moieties in the 2,4,5,7-tetraradical are greater and differ only slightly from each other. The slightly greater EA_2.30 for the 2,4-moiety in this tetraradical partially rationalizes the greater reactivity of this moiety when compared to the 5,7-moiety in the tetraradical.