Sequential radical and cationic reactivity at separated sites within one molecule in solution.

Distonic radical cations (DRCs) with spatially separated charge and radical sites are expected to show both radical and cationic reactivity at different sites within one molecule. However, such "dual" reactivity has rarely been observed in the condensed phase. Herein we report the isolation of crystalline 1λ2,3λ2-1-phosphonia-3-phosphinyl-cyclohex-4-enes 2a,b˙+, which can be considered delocalized DRCs and were completely characterized by crystallographic, spectroscopic, and computational methods. These DRCs contain a radical and cationic site with seven and six valence electrons, respectively, which are both stabilized via conjugation, yet remain spatially separated. They exhibit reactivity that differs from that of conventional radical cations (CRCs); specifically they show sequential radical and cationic reactivity at separated sites within one molecule in solution.

The case of a µ2-P aromatic phosphinine as a 4-electron donor forming σ- and π-three-center-two-electron bonds.

Profound insight into the electronic structures of occasionally observed µ2-P bridging phosphinines remains limited. In this work, we present the isolation and X-ray crystallographic characterization of a dimeric Rh(I) phosphinine complex exhibiting both η1-P and µ2-P phosphinine coordination modes. Variable temperature NMR analyses and DOSY spectrum measurement confirmed the presence of two types of fluxional phenomena in solution: η1-P phosphinine bonding and dissociation, and η1-P and µ2-P equilibrium. DFT calculations in conjunction with single crystal X-ray diffraction studies suggest that the µ2-P phosphinines donate four electrons via a σ-lone pair and a high-lying π-type electron pair, instead of two σ-lone pairs, forming σ- and π-three-center-two-electron bonds. The stronger π-type interactions lead to longer P-C bonds and larger negative coordination chemical shifts for µ2-P phosphinines. However, the binding interactions of µ2-P are thermodynamically weaker than those of η1-P. Reactivity studies further confirm the labile nature of the µ2-P phosphinine bonds, which could be easily converted to an η1-P phosphinine.

Room temperature stable E,Z-diphosphenes: their isomerization, coordination, and cycloaddition chemistry.

E,Z-isomers display distinct physical properties and chemical reactivities. However, investigations on heavy main group elements remain limited. In this work, we present the isolation and X-ray crystallographic characterization of N-heterocyclic vinyl (NHV) substituted diphosphenes as both E- and Z-isomers (L[double bond, length as m-dash]CH-P[double bond, length as m-dash]P-CH[double bond, length as m-dash]L, E,Z-2b; L = N-heterocyclic carbene). E-2b is thermodynamically more stable and undergoes reversible photo-stimulated isomerization to Z-2b. The less stable Z-isomer Z-2b can be thermally reverted to E-2b. Theoretical studies support the view that this E ↔ Z isomerization proceeds via P[double bond, length as m-dash]P bond rotation, reminiscent of the isomerization observed in alkenes. Furthermore, both E,Z-2b coordinate to an AuCl fragment affording the complex [AuCl(η2-Z-2b)] with the diphosphene ligand in Z-conformation, exclusively. In contrast, E,Z-2b undergo [2 + 4] and [2 + 1] cycloadditions with dienes or diazo compounds, respectively, yielding identical cycloaddition products in which the phosphorus bound NHV groups are in trans-position to each other. DFT calculations provide insight into the E/Z-isomerisation and stereoselective formation of Au(i) complexes and cycloaddition products.

Reversible Single Electron Redox Steps Convert Polycycles with a C3 P3 Core to a Planar Triphosphinine.

Reaction of the imidazolium-stabilized diphosphete-diide IDP with trityl phosphaalkyne affords a mixture which contains the molecules 1 a and 1 b with a central C3 P3 core, which formally carries a two-fold negative charge. In order to avoid the formation of an antiaromatic 8π electron system within a conjugated dianionic six-membered [C3 P3 ]2- ring, 1 a adopts a bicyclic [3.1.0] and 1 b a tricyclic [2.2.0.0] structure which are in a dynamic equilibrium. 1 a, b can be reversibly oxidized to a triphosphinine dication [5]2+ with a central flat aromatic six-membered C3 P3 ring. This two-electron redox reaction occurs in two single-electron transfer steps via the 7π-radical cation [4]⋅+ , which could also be isolated and fully characterized. The profound reversible structural change observed for the two-electron redox couple [5]2+ /1 a, b is in sharp contrast to the C6 H6 /[C6 H6 ]2- couple, which undergoes only a modest structural deformation.

Bis(imidazolium)-1,3-diphosphete-diide: A Building Block for FeC2 P2 Complexes and Clusters.

Reaction of the 6π-electron aromatic four-membered heterocycle (IPr)2 C2 P2 (1) (IPr=1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene) with [Fe2 CO9 ] gives the neutral iron tricarbonyl complex [Fe(CO)3 -η3 -{(IPr)2 C2 P2 }] (2). Oxidation with two equivalents of the ferrocenium salt, [Fe(Cp)2 ](BArF24 ), affords the dicationic tricarbonyl complex [Fe(CO)3 -η4 -{(IPr)2 C2 P2 }](BArF24 )2 (4). The one-electron oxidation proceeds under concomitant loss of one CO ligand to give the paramagnetic dicarbonyl radical cation complex [Fe(CO)2 -η4 -{(IPr)2 C2 P2 }](BArF24 ) (5). Reduction of 5 allows the preparation of the neutral dicarbonyl complex [Fe(CO)2 -η4 -{(IPr)2 C2 P2 }] (6). An analysis by various spectroscopic techniques (57 Fe Mössbauer, EPR) combined with DFT calculations gives insight into differences of the electronic structure within the members of this unique series of iron carbonyl complexes, which can be either described as electron precise or Wade-Mingos clusters.

Analysis of Genomic Alternative Splicing Patterns in Rat under Heat Stress Based on RNA-Seq Data.

Heat stress is one of the most severe challenges faced in livestock production in summer. Alternative splicing as an important post-transcriptional regulation is rarely studied in heat-stressed animals. Here, we performed and analyzed RNA-sequencing assays on the liver of Sprague-Dawley rats in control (22 °C, n = 5) and heat stress (4 °C for 120 min, H120; n = 5) groups, resulting in the identification of 636 differentially expressed genes. Identification analysis of the alternative splicing events revealed that heat stress-induced alternative splicing events increased by 20.18%. Compared with other types of alternative splicing events, the alternative start increased the most (43.40%) after heat stress. Twenty-eight genes were differentially alternatively spliced (DAS) between the control and H120 groups, among which Acly, Hnrnpd and mir3064 were also differentially expressed. For DAS genes, Srebf1, Shc1, Srsf5 and Ensa were associated with insulin, while Cast, Srebf1, Tmem33, Tor1aip2, Slc39a7 and Sqstm1 were enriched in the composition of the endoplasmic reticulum. In summary, our study conducts a comprehensive profile of alternative splicing in heat-stressed rats, indicating that alternative splicing is one of the molecular mechanisms of heat stress response in mammals and providing reference data for research on heat tolerance in mammalian livestock.

Cyano(triphenylsilyl)phosphanide as a Building Block for P,C,N Conjugated Molecules.

The cyano(triphenylsilyl)phosphanide anion was prepared as a sodium salt from 2-phosphaethynolate. The electronic structure of this new cyano(silyl)phosphanide was studied via computational methods and its reactivity investigated using various electrophiles and Lewis acids, demonstrating its P- and N-nucleophilicity. The ambident reactivity is in agreement with computations. The silyl group also shows lability and therefore the cyano(silyl)phosphanide can be considered as a phosphacyanamide synthon, [PCN]2- , and serves as building block for the transfer of a PCN moiety.

Reversible Stereoisomerization of 1,3-Diphosphetane Frameworks Revealed by a Single-Electron Redox Approach.

The discovery of pyramidal inversion has continued to impact modern organic and organometallic chemistry. Sequential alkylation reactions of an N-heterocyclic carbene (NHC) ligated dicarbondiphosphide 1 with RI (R = Me, Et, or iBu) and ZnMe2 give rise to the highly stereoselective synthesis of cis-1,3-diphosphetanes 3. cis-3 is conformationally favorable at room temperature, whereas inversion to trans-3 is observed at 110 °C. One-electron oxidation of cis-3 with Fc+(BArF) (Fc = [Fe(C5H5)2]; BArF = [B(3,5-(CF3)2C6H3)4)]-) leads to the stereoselective formation of trans-1,3-diphosphetane radical cation salts 3•+(BArF), which can be reversibly transformed to cis-3 upon one-electron reduction. Salts 3•+(BArF) represent the first examples of 1,3-diphosphetane radical cations. These results provide a potential application of planar four-membered heterocycle-based building blocks for electrically fueled molecular switches.

A Room-Temperature Stable Distonic Radical Cation.

Distonic radical cations (DRCs) with spatially separated charge and radical sites have, so far, largely been observed by gas-phase mass spectrometry and/or matrix isolation spectroscopy work. Herein, we disclose the isolation of a crystalline dicarbondiphosphide-based ß-distonic radical cation salt 3.+ (BARF) (BARF=[B(3,5-(CF3 )2 C6 H3 )4 )]- ) stable at room temperature and formed by a one-electron-oxidation-induced intramolecular skeletal rearrangement reaction. Such a species has been validated by electron paramagnetic resonance (EPR) spectroscopy, single-crystal X-ray diffraction, UV/Vis spectroscopy and density functional theory (DFT) calculations. Compound 3.+ (BARF) exhibits a large majority of spin density at a two-coordinate phosphorus atom (0.74 a.u.) and a cationic charge located predominantly at the four-coordinate phosphorus atom (1.53 a.u.), which are separated by one carbon atom. This species represents an isolable entity of a phosphorus radical cation that is the closest to a genuine phosphorus DRC to date.

Facile addition of E-H bonds to a dicarbondiphosphide.

Charge transfer at P atoms in an N-heterocyclic carbene stabilized 6π-electron aromatic dicarbondiphosphide 1 has been observed upon interaction with a variety of small molecule substrates that feature a polar E-H bond (E = C, N, and O). As a result, these P atoms exhibit fleeting nucleophilicity and electrophilicity behaving as potential independent active sites, which effect the spontaneous addition of E-H bonds leading to a series of unsymmetrical 1,3-diphosphetane frameworks bearing P-C (2), P-N (6 and 7), and P-O bonds (8b, 8c, and 9). In addition, 1,3-diphosphetanium salts have been achieved when X-type substituents are weakly coordinating (i.e. [(CN)2CH]- (3), I- (4), and [(PhOH)2PhO]- (10)). The mechanisms of such transformations are investigated using density functional theory calculations.

N-Heterocyclic Carbene Stabilized Dicarbondiphosphides: Strong Neutral Four-Membered Heterocyclic 6π-Electron Donors.

In contrast to cyclic π-conjugated hydrocarbons, the coordination chemistry of inorganic heterocycles is less developed. Dicarbondiphosphides stabilized by N-heterocyclic carbenes (NHCs) NHC→C2 P2 ←NHC (1 a,b) (NHC=IPr or SIPr) contain a four-membered C2 P2 ring with an aromatic 6π-electron configuration. These heterocycles coordinate to a variety of complex fragments with metals from groups 6, 9, and 10, namely [M0 (CO)3 ] (M=Cr, Mo), [CoI (CO)2 ]+ , or [NiII Br2 ], through an η4 -coordination mode, leading to complexes 2 a,b, 3 a,b, 5 a,b, and 6 a,b, respectively. These complexes were characterized by X-ray diffraction methods using single crystals, IR spectroscopy, and DFT calculations. In combination these methods indicate that 1 a,b behave as exceptionally strong 6π-electron donors.

Phosphanyl Cyanophosphide Salts: Versatile PCN Building Blocks.

The facile preparation of alkali salts of phosphanyl cyanophosphides [NHP-PCN]- (NHP=N-heterocyclic phosphenium) is reported. Their formation is achieved by isoelectronic replacement of O for [N]- in the phosphaketenes NHP-PCO using alkaline hexamethyldisilazide M[N(SiMe3 )2 ] (M=Na, K) as reagent. The new anionic entities are versatile PCN building blocks which allow the formation of a diversity of new cyanophosphine derivates including the first example of a PCNB hetero-cumulene and a PCN-ligated transition metal complex.

Making the unconventional µ2-P bridging binding mode more conventional in phosphinine complexes.

Phosphinines, as aromatic heterocycles, usually engage in coordination as η1-P σ-complexes or η6-phosphinine π-complexes. The µ2-P bridging coordination mode is rarely observed. With the aim to study the effect of different electronic configurations of phosphinines on the coordination modes, a series of anionic phosphinin-2-olates and neutral phosphinin-2-ols were prepared with moderate to high yield. Then the coordination chemistry of these two series was studied in detail towards coinage metals (Au(i) and Cu(i)). It is observed that the anionic phosphinin-2-olates possess a higher tendency to take a bridging position between two metal centers compared to the neutral phosphinin-2-ols. Based on these experimental findings bolstered by DFT calculations, some insight is gained on how the unconventional µ2-P phosphinine bridging coordination mode can be made more conventional and used for the synthesis of polynuclear complexes.

Corticosterone tissue-specific response in Sprague Dawley rats under acute heat stress.

Our study evaluated the physiological responses to acute heat stress in rats via body temperature and tissue corticosterone levels, and investigated the relative tissue response to heat stress based on corticosterone. Body temperature of rats under 22 °C (control) and 42 °C for 30 (H30), 60 (H60) and 120 min (H120) was measured. Correspondingly, corticosterone was analyzed in 11 tissues (adrenal, brain, heart, kidney, liver, lung, leg muscle, blood, stomach, spleen and small intestine). Analysis of variance and correlations were conducted on body temperature and corticosterone levels. The receiver operating characteristic (ROC) analyzed the thermo-sensitivity via corticosterone. Body temperature of rats in H30, H60 and H120 groups were higher (P < 0.05) than the control. Compared to the control, corticosterone levels of heart, stomach and small intestine at H30, corticosterone levels in adrenal, leg muscle and stomach at H60, and corticosterone levels in adrenal, heart, lung, stomach and small intestine at H120 differed (P < 0.05). The corticosterone in lung tissue was an excellent indicator of acute heat stress, with an area under the curve (AUC) of 1.00 at H60 and H120. In order to improve the prediction of acute heat stress, models combining corticosterone levels of multiple tissues reached an AUC of 1.00 for H30, and the sensitivity increased to 100% for H60 and H120. In conclusion, changes in the patterns and thermosensitivity of corticosterone levels associated with the duration of heat stress across body tissues were evidenced. The single and multi-organizational corticosterone models serve as indicators for evaluating heat stress across different time periods.

Bent Phosphaallenes With "Hidden" Lone Pairs as Ligands.

Phosphaheteroallenes R-P=C=L, with L = N-heterocyclic carbenes (NHCs), can be viewed to a certain extent as phosphaisonitriles stabilized with NHCs, R-P=C:←L. The suitability of these molecules as ligands for coinage-metal ions was investigated and coordination through the central carbon center was observed in most cases. A combination of experiments, spectroscopic methods, and DFT calculations indicates the presence of a hidden electron pair at the carbon center of R-P=C:←L. Remarkably, this lone pair also inserts intramolecularly in C-H bonds showing the carbene-type reactivity which is expected for phosphaisonitriles.

Metastable phosphorus neutral monoradical: a key intermediate in the bicyclic cage formation.

A key intermediate in the formation of a bicyclic cage formed between a biradical (LCP)2 (L = carbene) and an unsaturated substrate via a [2 + 2] cycloaddition reaction has been isolated and fully characterized including by X-ray diffraction analysis. The isolation of this intermediate proves that this cycloaddition reaction proceeds stepwise which is preferred over a concerted mechanism.

Pterostilbene alleviates hydrogen peroxide-induced oxidative stress via nuclear factor erythroid 2 like 2 pathway in mouse preimplantation embryos.

Pterostilbene (PTS) in blueberries is a phytoalexin with antioxidant properties. PTS exerts strong cytoprotective effects on various cells via Nuclear Factor Erythroid 2 like 2 (NFE2L2) pathway. We evaluated the antioxidant PTS treatment in mouse preimplantation embryos. In vitro culture media were supplemented with different concentrations of PTS. Treatment of zygotes with 0.25 µM PTS improved the development of day 4 blastocysts (P < 0.05). Moreover, H2O2 treatment significantly increased the reactive oxygen species level and reduced the glutathione level in mouse blastocyst, whereas PTS treatment counteracted these effects. The fluorescence intensity of apoptotic positive cell was higher in the H2O2 group than in the PTS group. Furthermore, PTS-treated embryos significantly increased the protein expression of NFE2L2 in the nucleus and decreased Kelch-like ECH-associated protein1 (KEAP1). PTS treatment significantly increased the expression of downstream target genes involved in the NFE2L2 pathway, such as catalase (CAT), heme oxygenase1 (HMOX1), glutathione peroxidase (GPX), and superoxide dismutase (SOD); these genes confer cellular protection. In addition, PTS treatment significantly increased the expression of anti-apoptotic B-cell lymphoma 2 (BCL2), with a concomitant reduction in the apoptotic Bcl-2-associated X protein (BAX) and Caspase-3 genes in the embryo. PTS treatment also increased the protein expression of BCL2 and reduced the protein expression of BAX in the mouse embryo. In conclusion, PTS activated NFE2L2 signaling pathway in the development of mouse embryos by altering downstream expression of genes involved in the antioxidant mechanisms and apoptosis.

Pterostilbene exerts a protective effect via regulating tunicamycin-induced endoplasmic reticulum stress in mouse preimplantation embryos.

Pterostilbene (PTS) mainly enriched in small fruits such as berries and grapes exerts an antioxidant effect. However, the protective effects of PTS against endoplasmic reticulum stress (ERS) have not yet been elucidated in mouse preimplantation embryo. ERS plays an important role in regulating the pathological and physiological processes, including embryonic development. We explored the protective effect of PTS on the tunicamycin (TM)-induced ERS in mouse preimplantation embryos. In vitro, culture medium was supplemented with different concentrations of TM and PTS. Our result indicated that treatment of zygotes with 0.5 µg/ml TM significantly decreased the development of day 4 blastocysts (P < 0.05), whereas 0.25 µM PTS supplementation improved the development rate of blastocysts. Moreover, TM treatment significantly increased (P < 0.05) the apoptotic index and reduced the total cell number of the blastocyst, whereas PTS treatment counteracted these effects. Additionally, TM potently increased expression levels of ERS-related proteins, such as GRP78, ATF6, PERK, p-Perk, IRE1, ATF4, and CHOP (P < 0.05). However, PTS and PTS + TM treatment decreased expression levels of ERS-related proteins (P < 0.05). Furthermore, expression level of the anti-apoptotic protein and gene BCL2 significantly decreased (P < 0.05) in TM-treated embryo but increased by PTS treatment (P < 0.05), whereas expression levels of the pro-apoptotic protein and gene BAX increased (P < 0.05) with TM but significantly decreased (P < 0.05) with co-treatment with PTS. In summary, PTS treatment significantly increased the development potential of mouse embryo by reduction of ERS.

Photoluminescent Phosphinine Cu(I) Halide Complexes: Temperature Dependence of the Photophysical Properties and Applications as a Molecular Thermometer.

Luminescent thermometers have attracted much attention, because of their fast response, high sensitivity, and noninvasive operation, relative to other traditional thermometers. The extensive studies on the temperature-dependent luminescent properties of Cu(I) complexes make this low-cost metal source a promising candidate as a component of thermometers. Herein, we prepared three luminescent phosphinine Cu(I) complexes whose emission lifetimes are precisely dependent on the temperature variations. For practical utilization, sensor films have been fabricated by doping these Cu(I) complexes into the matrices of polyacrylamide. These films not only exhibit excellent linear correlations between the temperature and emission lifetime over the wide range of 77-337 K, but also show high sensitivity (with the best one to -6.99 µs K-1). These are essential factors for the application in luminescent molecular thermometers. Moreover, the emission mechanism for these Cu(I) complexes are rationalized by the combination of experimental and theoretical results.

Bismesitoylphosphinic Acid (BAPO-OH): A Ligand for Copper Complexes and Four-Electron Photoreductant for the Preparation of Copper Nanomaterials.

Bismesitoylphosphinic acid, (HO)PO(COMes)2 (BAPO-OH), is an efficient photoinitiator for free-radical polymerizations of olefins in aqueous phase. Described here are the structures of various copper(II) and copper(I) complexes with BAPO-OH as the ligand. The complex CuII (BAPO-O)2 (H2 O)2 is photoactive, and under irradiation with UV light in aqueous phase, it serves as a source of metallic copper in high purity and yield (>80 %). Simultaneously, the radical polymerization of acrylates can be initiated and allows the preparation of nanoparticle/polymer nanocomposites in which the metallic Cu nanoparticles are protected against oxidation. The determination of the stoichiometry of the photoreductions suggests an almost quantitative conversion from CuII into Cu0 with half an equivalent of BAPO-OH, which serves as a four-electron photoreductant.