Electrophilic aromatic substitution reactions of compounds with Craig-Möbius aromaticity.

Electrophilic aromatic substitution (EAS) reactions are widely regarded as characteristic reactions of aromatic species, but no comparable reaction has been reported for molecules with Craig-Möbius aromaticity. Here, we demonstrate successful EAS reactions of Craig-Möbius aromatics, osmapentalenes, and fused osmapentalenes. The highly reactive nature of osmapentalene makes it susceptible to electrophilic attack by halogens, thus osmapentalene, osmafuran-fused osmapentalene, and osmabenzene-fused osmapentalene can undergo typical EAS reactions. In addition, the selective formation of a series of halogen substituted metalla-aromatics via EAS reactions has revealed an unprecedented approach to otherwise elusive compounds such as the unsaturated cyclic chlorirenium ions. Density functional theory calculations were conducted to study the electronic effect on the regioselectivity of the EAS reactions.

Isolation, Reactivity, and Tunable Properties of a Strained Antiaromatic Osmacycle.

Strain and antiaromaticity in compounds are recognized as two substantial destabilizing features, and consequently, realization of dual destabilizing features in a single molecule is challenging and far more difficult in a single ring. Moreover, transformation of an antiaromatic framework to different antiaromatic or aromatic species is a significant subject in antiaromatic chemistry and has attracted increasing interest. In this work, we isolated a highly strained antiaromatic metallacycle in which a cyclic metal vinylidene unit is embedded. Computational studies revealed its ring strain energies and antiaromatic character and showed that the metal incorporation and the phosphonium substituents play a crucial role in its stabilization. The mechanism of its formation has been illustrated by density functional theory (DFT) calculations and the isolation of a key intermediate. We further discovered diverse reactivities and structural reshuffling of this unusual strained antiaromatic complex according to its two destabilizing characters. We obtained two isomers of metallaindenes fused with oxiranes from the direct oxidation of the metal vinylidene or by nucleophilic addition to an isolated metallacyclocumulene formed by the reaction of metal vinylidene with hydroxide ion, achieving a reconfiguration of the antiaromatic framework. Transformations of the antiaromatic metallacycle by electrophiles to various aromatic metallaindynes have been achieved, and that a condensed Fukui function was employed to confirm the regioselectivity of the electrophilic additions, and the acid/base-induced aromaticity switch along with tunable photophysical properties were investigated. These interesting transformations not only enrich the chemistry of metal vinylidenes and antiaromatics and could also perform potentially as switchable optical materials.

Synthesis and Characterization of a Rhenanaphthalene Isomer.

Exploration of organometallic metallacycles has led to the development of various polycyclic compounds with fascinating structures, which could be used as functional materials. In this work, a new rhenanaphthalene isomer was isolated from the reaction of ReH5 (PMe2 Ph)3 with o-ethynylphenyl alkyne in the presence of excess HCl. Its structure was then identified using the single-crystal X-ray diffraction and NMR spectroscopy. DFT studies suggest that its formation involves two protonation reactions and two migration reactions. This new rhenanaphthalene isomer enriches the family of metallacycles.

Selective Difunctionalization of Unactivated Aliphatic Alkenes Enabled by a Metal-Metallaaromatic Catalytic System.

The design of organometallic catalysts is crucial in the development of catalytic reactions. Herein, we describe a heterometallic [Os-Cu] complex with the characteristics of bimetallics, metallaaromatics, and pincer complexes. This complex serves as a highly effective catalyst for selective amino- and oxyselenation of unactivated alkenes. More than 80 examples including challenging substrates of unsymmetric aliphatic alkenes and amine-based nucleophiles in such reactions are provided. These reactions produce 1,2-difunctionalized products with good yields and high levels of chemo-, regio-, and stereoselectivity. Our studies revealed the following: (i) The usually inert osmium center activates the N- or O-centered nucleophiles. (ii) The copper-osmium bonding and its cooperative effects play essential roles in control the selectivity by bringing the reaction components into close proximity. (iii) The metallaaromatic moiety helps to stabilize the intermediate. These findings provide a versatile platform for catalyst design based on metal-metallaaromatic cooperative effects that have not been attained previously with bimetallic complexes.

Synthesis of (Thio)Furan-Fused Phospholes via Phosphonation Cyclization and a Base-Promoted Phospha-Friedel-Crafts Reaction.

Herein, we developed a novel strategy for synthesizing ladder (thio)furan-fused phospholes via intermolecular phosphonation cyclization and a base-promoted phospha-Friedel-Crafts reaction under mild conditions. The starting substrates are readily available phosphinic acids and easy-to-handle alkynes. The details of the reaction mechanism were further rationalized using theoretical calculations. This protocol can be widely applied to synthesize furan- and thiofuran-fused phospholes as well as the corresponding large π-extended derivatives, which are of great interest in the domain of organic functional materials.

Metallaaromatic Chemistry: History and Development.

Since the prediction of the existence of metallabenzenes in 1979, metallaaromatic chemistry has developed rapidly, due to its importance in both experimental and theoretical fields. Now six major types of metallaromatic compounds, metallabenzenes, metallabenzynes, heterometallaaromatics, dianion metalloles, metallapentalenes and metallapentalynes (also termed carbolongs), and spiro metalloles, have been reported and extensively studied. Their parent organic analogues may be aromatic, non-aromatic, or even anti-aromatic. These unique systems not only enrich the large family of aromatics, but they also broaden our understanding and extend the concept of aromaticity. This review provides a comprehensive overview of metallaaromatic chemistry. We have focused on not only the six major classes of metallaaromatics, including the main-group-metal-based metallaaromatics, but also other types, such as metallacyclobutadienes and metallacyclopropenes. The structures, synthetic methods, and reactivities are described, their applications are covered, and the challenges and future prospects of the area are discussed. The criteria commonly used to judge the aromaticity of metallaaromatics are presented.

Site-Specific Photochemical Desaturation Enables Divergent Syntheses of Illicium Sesquiterpenes.

Desaturation of unactivated alkanes remains a challenging yet desirable strategy to make olefins. The Illicium sesquiterpenes usually possess highly oxygenated cage-like architectures, and some of them exhibit prominent neurotrophic effects. Here, we disclose a unique photochemical desaturation strategy for the efficient, highly stereocontrolled total syntheses of five Illicium sesquiterpenes from inexpensive (R)-pulegone, featuring a 13-step gram-scale synthesis of (-)-merrilactone A. The efficiency of the syntheses derives from an expedient construction of a tetracyclic framework via two annulations, a site-specific photoinduced single-step desaturation in a complex hydrocarbon system, and diverse oxygenation manipulations around the resultant olefin intermediate. This work highlights how late-stage desaturation can dramatically streamline the synthesis of complex terpenes and diverse non-natural analogues for establishing the structure-activity relationship and elucidating their molecular mechanisms of bioactivity.

Tuning an Electrode Work Function Using Organometallic Complexes in Inverted Perovskite Solar Cells.

Low-work-function (WF) metals (including silver (Ag), aluminum (Al), and copper (Cu)) used as external cathodes in inverted perovskite solar cells (PSCs) encounter oxidation caused by air exposure and halogen-diffusion-induced corrosion, which threaten the long-term stability of the device. The cathode interlayer (CIL) has shown promise in reducing the metal WF and thus boosting the device power conversion efficiency (PCE). However, it remains a challenge for current CIL materials to enable high-WF metals (e.g., Au) to be used as cathodes to achieve PSCs with a superior PCE and long-term stability. Here, we use a series of synthesized (carbolong-derived) organometallic complexes as CILs to tune the electrode WF in inverted PSCs. Density functional theory calculations and surface characterizations show that the organometallic complexes that contain anions and cations are prone to form anion-cation dipoles on the metal surface, hence drastically reducing the metal's WF. Photovoltaic devices based on a Ag cathode, which was modified with these organometallic complexes, received a boosted PCE up to 21.29% and a remarkable fill factor that reached 83.52%, which are attributed to the dipole-enhanced carrier transport. The environmental stability of PSCs was further improved after employing Au as a cathode with these organometallic complexes, and the modified devices exhibited no efficiency loss after 4080 h storage measurements.

CYP2C9 inhibits the invasion and migration of esophageal squamous cell carcinoma via downregulation of HDAC.

Cytochrome P450 2C9 (CYP2C9) is involved in the metabolism of cancer drugs and exogenous carcinogens. In our study, CYP2C9 was downregulated in multiple cohorts of human esophageal squamous cell carcinoma (ESCC). Until now, its role and epigenetic regulation of CYP2C9 repression in ESCC remain poorly understood. CYP2C9 repression in collected ESCC patient tumor tissues was demonstrated by RT-qPCR and Western blot. The histone acetylation level was carried out by the treatment of histone deacetylase inhibitor TSA and RNA interference. Epigenetic analysis revealed that the increased expression of CYP2C9 in KYSE-150 and TE1 cells was characterized by inhibition of HDAC8 and HDAC1, respectively. TSA decreased the levels of HDAC occupancy around CYP2C9 promoter region greatly. Overexpression of CYP2C9 reduced the invasion and migration of ESCC cells.

Merging C-H Vinylation with Switchable 6π-Electrocyclizations for Divergent Heterocycle Synthesis.

Pyridinium-containing polyheterocycles exhibit distinctive biological properties and interesting electrochemical and optical properties and thus are widely used as drugs, functional materials, and photocatalysts. Here, we describe a unified two-step strategy by merging Rh-catalyzed C-H vinylation with two switchable electrocyclizations, including aza-6π-electrocyclization and all-carbon-6π-electrocyclization, for rapid and divergent access to dihydropyridoisoquinoliniums and dihydrobenzoquinolines. Through computation, the high selectivity of aza-electrocyclization in the presence of an appropriate "HCl" source under either thermal conditions or photochemical conditions is shown to result from the favorable kinetics and symmetries of frontier orbitals. We further demonstrated the value of this protocol by the synthesis of several complex pyridinium-containing polyheterocycles, including the two alkaloids berberine and chelerythrine.

Multicenter-Bond-Based Quantum Interference in Charge Transport Through Single-Molecule Carborane Junctions.

Molecular components are vital to introduce and manipulate quantum interference (QI) in charge transport through molecular electronic devices. Up to now, the functional molecular units that show QI are mostly found in conventional π- and σ-bond-based systems; it is thus intriguing to study QI in multicenter bonding systems without both π- and σ-conjugations. Now the presence of QI in multicenter-bond-based systems is demonstrated for the first time, through the single-molecule conductance investigation of carborane junctions. We find that all the three connectivities in carborane frameworks show different levels of destructive QI, which leads to highly suppressed single-molecule conductance in para- and meta-connected carboranes. The investigation of QI into carboranes provides a promising platform to fabricate molecular electronic devices based on multicenter bonds.

Metallapentalenofuran: Shifting Metallafuran Rings Promoted by Substituent Effects.

Bulky substituents play important roles in controlling the reaction pathways or producing selected products. This work reports that the shift of metallafuran rings in a metallapentalenofuran complex can be promoted by the substituent effect via a reversible C-H bond reductive elimination and oxidative addition. The starting osmapentalyne, a so-called 7-carbon carbolong complex, was produced by the oxidation of a metallapentalenofuran with FeCl3 . It was then allowed to react with nucleophiles, followed by a C-H activation, to give the aforementioned metallapentalenofuran complex. This work enriches the family of carbolong complexes and reveals a new strategy to promote, but not prevent reactions by the bulky substituents.

Reactions of Isocyanides with Metal Carbyne Complexes: Isolation and Characterization of Metallacyclopropenimine Intermediates.

η2-Iminoketenyl species have often been postulated as the intermediates in nucleophile-induced carbyne-isocyanide C-C coupling processes. However, such species are elusive. Here we report direct formation of η2-iminoketenyl complexes from reactions of metallapentalyne with isocyanides. Our studies show that steric effects of N-substituents of the isocyanides play an important role in the stability of the three-membered metallacycles of the η2-iminoketenyl complexes. Sterically bulky isocyanides, such as tert-butyl or 1-adamantyl isocyanides, inhibit bending at the isocyanide nitrogen atoms, a requirement for formation of η2-iminoketenyl structures. Reactions of metallapentalyne with excess isocyanide allow the metal-bridged metallaindene derivativesto be isolated as a result of the isocyanide insertion into the M-Cα σ bond of metallapentalyne.

Metallapentalenofurans and Lactone-Fused Metallapentalynes.

Metalla-aromatics are attractive species because they exhibit the properties of both organometallics and aromatics. Reported metal-bridged polycyclic aromatic complexes, as well as Möbius aromatic species, are still rare. Herein, we present the construction of two new metal-bridged polycyclic aromatic frameworks, α-metallapentalenofurans and lactone-fused metallapentalynes, by the reactions of osmapentalyne with terminal aryl alkynes in the presence of H2 O or HBF4 /H2 O, respectively. DFT calculations show that the α-metallapentalenofurans possess rare planar Craig-type Möbius aromaticity derived from the 11-center-12-electron dπ -pπ π-conjugation. This study offers a new route for the construction of polycyclic metalla-aromatics as well as planar Möbius aromatic species.

Total Synthesis of Aplydactone by a Conformationally Controlled C-H Functionalization.

A concise, protecting-group-free total synthesis of the unusual brominated sesquiterpene aplydactone is described. Our synthesis features a [2+2] photocycloaddition, a Wolff ring contraction, an unusual remote C-H functionalization to establish the highly strained tetracyclic core, and a hydrogen-atom transfer (HAT) reaction to access the bromine-containing stereocenter. A finely tuned conformation of the α-diazoketone precursor is the key for the success of the late-stage transannular C-H insertion to deliver a bridged six-membered ring and a quaternary stereocenter (C6) between two quaternary carbon atoms (C1 and C7).

Characterization, sequencing and comparative genomic analysis of vB_AbaM-IME-AB2, a novel lytic bacteriophage that infects multidrug-resistant Acinetobacter baumannii clinical isolates.

BACKGROUND: With the use of broad-spectrum antibiotics, immunosuppressive drugs, and glucocorticoids, multidrug-resistant Acinetobacter baumannii (MDR-AB) has become a major nosocomial pathogen species. The recent renaissance of bacteriophage therapy may provide new treatment strategies for combatting drug-resistant bacterial infections. In this study, we isolated a lytic bacteriophage vB_AbaM-IME-AB2 has a short latent period and a small burst size, which clear its host's suspension quickly, was selected for characterization and a complete genomic comparative study. RESULTS: The isolated bacteriophage vB_AbaM-IME-AB2 has an icosahedral head and displays morphology resembling Myoviridae family. Gel separation assays showed that the phage particle contains at least nine protein bands with molecular weights ranging 15-100 kDa. vB_AbaM-IME-AB2 could adsorb its host cells in 9 min with an adsorption rate more than 99% and showed a short latent period (20 min) and a small burst size (62 pfu/cell). It could form clear plaques in the double-layer assay and clear its host's suspension in just 4 hours. Whole genome of vB_AbaM-IME-AB2 was sequenced and annotated and the results showed that its genome is a double-stranded DNA molecule consisting of 43,665 nucleotides. The genome has a G + C content of 37.5% and 82 putative coding sequences (CDSs). We compared the characteristics and complete genome sequence of all known Acinetobacter baumannii bacteriophages. There are only three that have been sequenced Acinetobacter baumannii phages AB1, AP22, and phiAC-1, which have a relatively high similarity and own a coverage of 65%, 50%, 8% respectively when compared with our phage vB_AbaM-IME-AB2. A nucleotide alignment of the four Acinetobacter baumannii phages showed that some CDSs are similar, with no significant rearrangements observed. Yet some sections of these strains of phage are nonhomologous. CONCLUSION: vB_AbaM-IME-AB2 was a novel and unique A. baumannii bacteriophage. These findings suggest a common ancestry and microbial diversity and evolution. A clear understanding of its characteristics and genes is conducive to the treatment of multidrug-resistant A. baumannii in the future.

Characterization of the morphology and genome of an Escherichia coli podovirus.

Escherichia coli is an important opportunistic pathogen. It can cause sepsis and severe infection. The application of lytic bacteriophages to treat infectious diseases is an alternative to antibiotics. A lytic Escherichia coli phage, designated IME-EC2, was isolated from hospital sewage. Transmission electron microscopy revealed that IME-EC2 to be a member of the family Podoviridae. It had a 60-nm head and a 15-nm tail. Here, we present the complete genome sequence of this phage, which consists of 41,510 bp with an overall G+C content of 59.2 %. A total of 60 coding sequences (CDS) were identified, and the phage genome does not contain any tRNA genes. Forty percent of the unknown CDSs are unique to IME-EC2. This phage does not show significant similarity to other phages at the DNA level, which suggests that IME-EC2 could be a novel phage. One of the unique features identified in the IME-EC2 genome was a gene coding for a putative colanic-acid-degrading protein, which could allow the phage to degrade bacterial capsule and biofilms. Another unique feature is that IME-EC2 does not contain a terminase small subunit, which suggests that this phage may have a unique packaging mechanism. The present work provides novel information on phages and shows that this lytic phage or its products could be exploited to destroy bacterial biofilms and pathogenic E. coli.

Metallacyclobutadienes: Intramolecular Rearrangement from Kinetic to Thermodynamic Isomers.

Metallacyclobutadienes (MCBDs) are key intermediates of alkyne metathesis reactions. There are in principle two isomerization pathway from kinetic to thermodynamic MCBDs, intermolecular and intramolecular. However, systems that simultaneously isolate two kinds of MCBD isomers have not been achieved, thus restricting the mechanistic studies of the isomerization. Here the reactivity of a metallapentalyne that contains an M≡C bond within the aromatic ring, with alkynes to afford a series of MCBD-fused metallapentalenes is studied. In some cases, both kinetic and thermodynamic products are isolated in the same system, which has never been observed in previous MCBD reactions. Furthermore, the isomerization of MCBD-fused metallapentalenes is investigated both experimentally and theoretically, indicating that it is an intramolecular process involving a metallatetrahedrane (MTd) intermediate. This research provides experimental evidence demonstrating that one MCBD can undergo intramolecular rearrangement to transform into another.

Propargylic Dialkyl Effect for Cyclobutene Formation through Ir(III)-Catalyzed Cycloisomerization of 1,6-Enynes.

The propargylic dialkyl effect (PDAE) has a significant impact on the cyclization reaction of enynes, partly reflected in changing the types of products. Herein, we described the influence of the propargylic dialkyl effect on the Ir(III)-catalyzed cycloisomerization of 1,6-enynes to provide strained cyclobutenes. A series of substituted 1,6-enynes were proved to be excellent substrate candidates in the presence of [Cp*IrCl2]2 in toluene. Mechanistic investigation, based on deuterium labeling experiments and control experiments, indicated that the propargylic dialkyl effect might boost C(sp)-H activation by preventing the coordination of active iridium species to the C(sp)≡C(sp) bond of enynes. This finding contributes to the fundamental understanding of enyne cyclization reactions and offers valuable insight into the propargylic dialkyl effect.

Design, synthesis and biological evaluation of N-sulfonyl homoserine lactone derivatives as inhibitors of quorum sensing in Chromobacterium violaceum.

A novel series of N-sulfonyl homoserine lactone derivatives 5a-l has been designed, synthesized and evaluated for quorum sensing inhibitory activities towards violacein production. Of the compounds synthesized, compound 5h was found to possess an excellent level of enantiopurity (99.2% e.e.). The results indicated that compounds bearing an ortho substituent on their phenyl ring exhibited excellent levels of inhibitory activity against violacein production. Compounds 5h and 5k in particular, with IC50 values of 1.64 and 1.66 µM, respectively, were identified as promising lead compounds for further structural modification.