Controlled Ring Opening of a Tetracyclic Tetraphosphane with Twofold Metallocene Bridging.

A direct route to a doubly ferrocene bridged tetracyclic tetraphosphane 1 was developed via reductive coupling of Fe(CpPCl2)2 (2 a), where a chlorine terminated linear P4-compound 3 could be identified as an intermediate. Selective P-P bond activation was further achieved by reacting 1 with elemental selenium or [Cp*Al]4, where regioselective insertion of Se or Al atoms resulted in ferrocenylene bridged [P4Se] (4) or [P4Al] (7) moieties. Compound 7 can be transformed to a hydrogen terminated linear P4 species, 8, with protic solvents. Methylation of compound 1 with MeOTf, proceeds via intermediate formation of monomethylated species 5, which gradually produced Me2-terminated dicationic 6, again containing a linear P4-unit. Besides spectroscopic characterization, the structural details of compounds 1, 4, 6, and 8 could be determined by SC-XRD. Moreover, DFT calculations were used to rationalize the reactivity of 1, derived compounds and intermediates. As a key feature, 1 undergoes ring opening polymerization to a linear polyphosphane 9.

E and M SARS-CoV-2 membrane protein expression and enrichment with plant lipid droplets.

Plants are gaining traction as a cost-effective and scalable platform for producing recombinant proteins. However, expressing integral membrane proteins in plants is challenging due to their hydrophobic nature. In our study, we used transient and stable expression systems in Nicotiana benthamiana and Camelina sativa respectively to express SARS-CoV-2 E and M integral proteins, and target them to lipid droplets (LDs). LDs offer an ideal environment for folding hydrophobic proteins and aid in their purification through flotation. We tested various protein fusions with different linkers and tags and used three dimensional structure predictions to assess their effects. E and M mostly localized in the ER in N. benthamiana leaves but E could be targeted to LDs in oil accumulating tobacco when fused with oleosin, a LD integral protein. In Camelina sativa seeds, E and M were however found associated with purified LDs. By enhancing the accumulation of E and M within LDs through oleosin, we enriched these proteins in the purified floating fraction. This strategy provides an alternative approach for efficiently producing and purifying hydrophobic pharmaceuticals and vaccines using plant systems.

Gradual Coordination and Reversible P-P Bond Activation of a P3 -Unit with Transition Metal Carbonyls.

Coordination of a stereochemically defined P3 -chain to a series of transition metal carbonyls [M(CO)x ]z- (M = Mn (x = 5, z = 1), Fe (x = 4, z = 2) or Co (x = 4, z = 1)) is explored using a [3]ferrocenophane scaffold. A gradual transition from η1 -, η2 - to Î·3 -coordination is observed where in the η2 -mode the terminal positions of the phosphorus chain are bridged. With an excess of cobalt carbonyl successive P-P bond activation and gradual separation of the central phosphorus atoms from the phosphorus chain has been observed. This process is reversible and with suitable reagents such as methyl lithium, the P3 -unit is regenerated in stereospecific manner. The bonding situation and steps of the gradual P-P bond activation are investigated by DFT calculations as well as experimental methods (e.g., NMR spectroscopy, X-ray crystallography).

At the limits of bisphosphonio-substituted stannylenes.

Donor stabilization of Sn(II) and Pb(II) halides with 1,1'-ferrocenylene bridged bisphosphanes has been explored for Fe(C5 H4 P(C6 H5 )2 )2 (dppf), and Fe(C5 H4 PH(C4 H9 ))2 . These bisphosphanes are reacted with SnBr2 and PbCl2 with and without additional Lewis acid (AlCl3 ) forming acyclic and cyclic donor adducts from which the latter represent bisphosphoniotetrylenes. Since dynamic exchange in solution is observed, characterization includes solution and solid-state NMR in addition to SC-XRD, amended by DFT calculations.

Iron(II) Complexes of P3 -Chain Ligands: Structural Diversity.

Iron(II) complexes containing ligands with a R2 P-P-PR2 unit were synthesized by metathesis reactions. With R=tBu, a mixture of two isomers is formed; in one of them, the terminal phosphorus binds to the Fe center (ylidic structure), while in the other one, the central P atom is linked to Fe. Starting from differently functionalized parent triphosphanes and corresponding functionalized Fe complexes, the ratio of isomers does not change. The outcome of the reaction and therefore the binding modes of the triphosphane ligands in the resulting compounds can be influenced by the size of the substituents. In the case of R=iPr a chelate complex is formed (both terminal P atoms are linked to the Fe center). Applying the mixed-substituted triphosphane, the ylidic structure of the resulting complex is preferred. The new compounds were characterized by NMR spectroscopy in solution and single-crystal X-ray diffraction in solid-state. The synthetic work was supported by DFT calculations.

Access to and reactions of P-functional 1,4-dihydro-1,4-diphosphinines fused to two TTF units.

P-Functional phosphanylated tetrathiafulvalenes 3a-f were synthesised via stepwise lithiation and phosphanylation of TTF derivatives, and then reacted with PCl3 to form the related P-chloro compounds 4a-f. Reactions of 4c-f with LDA resulted in the formation of the corresponding 1,4-dihydro-1,4-diphosphinines 5c-f. As a case in point, P-oxidation reactions of 5d,f with elemental chalcogens were performed, and the former were also converted into 1,4-dichloro-1,4-dihydro-1,4-diphosphinine 9f. The latter was reduced to form the related 1,4-diphosphinine 10f which could not be isolated but formed the corresponding 1,4-diphosphabarrelene 11f in a [4 + 2]-cycloaddition with 1-hexene. All compounds were characterised by multinuclear NMR spectroscopy and mass spectrometry and also by single crystal X-ray diffraction studies in some cases. Intensive cyclic voltammetry studies were performed for all isolated compounds with the special focus on using TTF units as sensors to study the substituent effects on oxidation potentials and, hence, the degree of electronic communication between redox active moieties in the bis-TTF species. E.g., 5d possesses four quasi-reversible one-electron oxidation steps thus forming a tetracation species at highest potential (+0.54 V vs. Fc+/0). Additionally, high level DFT calculations were undertaken to get a deeper understanding of various aspects of this novel combination of phosphorus and TTF chemistry.

Interplay between NIN-LIKE PROTEINs 6 and 7 in nitrate signaling.

NLP7 (NIN-LIKE-PROTEIN 7) is the major transcriptional factor responsible for the primary nitrate response (PNR), but the role of its homolog, NLP6, in nitrogen signaling and the interplay between NLP6 and NLP7 remain to be elucidated. In this study, we show that, like NLP7, nuclear localization of NLP6 via a nuclear retention mechanism is nitrate dependent, but nucleocytosolic shuttling of both NLP6 and NLP7 is independent of each other. Compared with single mutants, the nlp6nlp7 double mutant displays a synergistic growth retardation phenotype in response to nitrate. The transcriptome analysis of the PNR showed that NLP6 and NLP7 govern ∼50% of nitrate-induced genes, with cluster analysis highlighting 2 distinct patterns. In the A1 cluster, NLP7 plays the major role, whereas in the A2 cluster, NLP6 and NLP7 are partially functionally redundant. Interestingly, comparing the growth phenotype and PNR under high- and low-nitrate conditions demonstrated that NLP6 and NLP7 exert a more dominant role in the response to high nitrate. Apart from nitrate signaling, NLP6 and NLP7 also participated in high ammonium conditions. Growth phenotypes and transcriptome data revealed that NLP6 and NLP7 are completely functionally redundant and may act as repressors in response to ammonium. Other NLP family members also participated in the PNR, with NLP2 and NLP7 acting as broader regulators and NLP4, -5, -6, and -8 regulating PNR in a gene-dependent manner. Thus, our findings indicate that multiple modes of interplay exist between NLP6 and NLP7 that differ depending on nitrogen sources and gene clusters.

The Arabidopsis transcription factor NLP2 regulates early nitrate responses and integrates nitrate assimilation with energy and carbon skeleton supply.

Nitrate signaling improves plant growth under limited nitrate availability and, hence, optimal resource use for crop production. Whereas several transcriptional regulators of nitrate signaling have been identified, including the Arabidopsis thaliana transcription factor NIN-LIKE PROTEIN7 (NLP7), additional regulators are expected to fine-tune this pivotal physiological response. Here, we characterized Arabidopsis NLP2 as a top-tier transcriptional regulator of the early nitrate response gene regulatory network. NLP2 interacts with NLP7 in vivo and shares key molecular features such as nitrate-dependent nuclear localization, DNA-binding motif, and some target genes with NLP7. Genetic, genomic, and metabolic approaches revealed a specific role for NLP2 in the nitrate-dependent regulation of carbon and energy-related processes that likely influence plant growth under distinct nitrogen environments. Our findings highlight the complementarity and specificity of NLP2 and NLP7 in orchestrating a multitiered nitrate regulatory network that links nitrate assimilation with carbon and energy metabolism for efficient nitrogen use and biomass production.

Gradual Donor Stabilization of a Transient Ferrocene Bridged Bisphosphanyl Phosphenium Cation.

A transient phosphenium cation embedded into a [3]ferrocenophane scaffold was formed via chloride abstraction. The cation has been trapped with phosphane, carbene, and silylene donors resulting in stable adducts or bond activation of the ferrocenophane bridge. In the absence of donors, dimerization of the phosphenium cation to the corresponding dication is observed or P-C bond activation with migration of a substituent leading to a putative phosphoniodiphosphene. Using 1,3-di-tert-butylimidazol-2-silylene as the donor, further reaction of the initially formed chlorosilane leads to activation of a P-P bond of the ferrocenophane scaffold with ring expansion of the ansa-bridge. The donor formation and bonding situation are investigated by density functional theory calculations as well as experimental methods (e.g., NMR spectroscopy and X-ray crystallography).

Three-Component Reaction of 3-Formyl-6-Methylchromone, Primary Amines, and Secondary Phosphine Oxides: A Synthetic and Mechanistic Study.

A fast, mild, and efficient catalyst-free approach has been developed for the synthesis of chromonyl-substituted α-aminophosphine oxides by the three-component reaction of 3-formyl-6-methylchromone, primary amines, and secondary phosphine oxides at ambient temperature. Carrying out the reaction with aliphatic amines or aminoalcohols at a higher temperature (80 °C), phosphinoyl-functionalized 3-aminomethylene chromanones were formed instead of the corresponding chromonyl-substituted α-aminophosphine oxides. No reaction occurred when 3-formyl-6-methylchromone and secondary phosphine oxides were reacted with aromatic amines in the absence of any catalyst. Applying a basic catalyst, the formation of the phosphinoyl-functionalized 3-aminomethylene chromanones was observed; however, the reaction was not complete. Detailed experimental and quantum chemical studies were performed to study the transformation. Moreover, the in vitro cytotoxicity of phosphinoyl-functionalized 3-aminomethylene chromanones was also investigated in three different cell lines, such as human lung adenocarcinoma (A549), mouse fibroblast (NIH/3T3), and human promyelocytic leukemia (HL60) cells. Several derivatives showed modest activity against the human promyelocytic leukemia (HL60) cell line.

Conjugation between 3D and 2D aromaticity: does it really exist? The case of carborane-fused heterocycles.

Although several synthesized icosahedral carborane fused 2D π-ring systems are known, and even considerable conjugation has been noted between them in some cases, the phenomenon itself is not fully understood. Based on the results of our computational study, it can be concluded that the 2D aromatic character of the fused (exo) five-membered ring is low, even in cases where significant conjugation was proposed in previous studies. Moreover, the carborane moiety constricts the bonding properties of the exo ring, thus prohibiting or promoting different Lewis resonance structures. These results will shed further light on the design and electronic modulation of new carborane-based materials.

A new access to diazaphospholes via cycloaddition-cycloreversion reactions on triazaphospholes.

A novel bis-CF3-substituted diazaphosphole was synthesized selectively from hexafluoro-2-butyne and a 3H-1,2,3,4-triazaphosphole derivative. The [4+2] cycloaddition and subsequent cycloreversion reaction under elimination of pivaloyl nitrile affords the product in high yield. The heterocycle coordinates via the phosphorus atom to a W(CO)5-fragment and shows stronger π-accepting properties than the triazaphosphole.

o-Carborane-based fluorophores as efficient luminescent systems both as solids and as water-dispersible nanoparticles.

A set of o-carborane-appended π-conjugated fluorophores and their light-emitting properties in the solid state are reported. The aggregation-induced emission enhancement (AIEE) exhibited for one of the fluorenyl derivatives paved the way to successfully preparing o-carborane-containing organic nanoparticles (NPs) homogeneously dispersed in aqueous media that maintain their luminescence properties. Notably, NPs processed as thin films also show high fluorescence efficiency, suggesting potential optical and optoelectronic applications.

Reversible Redox Chemistry of Anionic Imidazole-2-thione-Fused 1,4-Dihydro-1,4-diphosphinines.

Anionic 1,4-dihydro-1,4-diphosphinines were synthesized from tricyclic 1,4-diphosphinines and isolated as blue powdery salts M[2a-2c]. Reaction of solutions of these monoanions with iodomethane led to P-methylated compounds 3a-3c. An oxidation/reduction cycle was examined, starting from solutions of K[2a] via P-P coupled product 4a and back to K[2a], and the recyclability and redox chemistry of this cycle were confirmed by experimental and simulated cyclic voltammetry analysis, which is proposed as a potential 2-electron cathode for rechargeable cells. TD-DFT studies were used to examine species that might be involved in the process.

Toward a 1,4-Diphosphinine-Based Molecular CPS-Ternary Compound.

Synthesis of the tricyclic 1,3-dithiole-2-thione-derived 1,4-dihydro-1,4-diphosphinine is presented using a base-induced ring formation protocol and chloro(diethylamino)(1,3-dithiole-2-thion-4-yl)phosphane as the starting point. P-oxidation reactions of dihydrodiphosphinine by chalcogens led to bis(P-oxide), bis(P-sulfide), or bis(P-selenide), respectively; all tricyclic compounds were obtained as cis/trans mixtures. 1,4-Dihydro-1,4-diphosphinine was converted into 1,4-dichloro-1,4-dihydro-1,4-diphosphinine. This compound is almost insoluble in organic solvents, furnished selectively the trans-bis(amino) derivative upon a 2-fold P-substitution reaction with the weak nucleophile potassium bis(trimethylsilyl)amide, and reacted also with alcohols ROH (R = nBu, iPr, tBu) to give cis/trans mixtures of the corresponding bis(alkoxy) derivatives. Furthermore, the dichloro derivative could be reduced to a 1,4-diphosphinine using PnBu3, but, unfortunately, the stubbornly insoluble product could be neither purified nor crystallized. Despite this, we achieved a thermal [4 + 2] cycloaddition reaction of this first CPS-ternary compound with diethylacetylene dicarboxylate to obtain the corresponding diphosphabarrelene, thus providing indirect evidence for the aromatic tricyclic diphosphinine. Detailed density functional theory studies on the formation of 1,4-diphosphinine provided insights into formation pathways as well as NMR, IR, and UV/vis data.

Phosphetes via Transition Metal Free Ring Closure - Taking the Proper Turn at a Thermodynamic Crossing.

A transition metal free route to phosphetes featuring an exocyclic alkene unit is presented. In this approach phosphanides are added to a variety of diynes generating phosphaallylic intermediates which depending on the reaction conditions transform either to phosphetes or the corresponding phospholes. Investigation of the reaction mechanism by combined quantum chemical and experimental means identifies phosphole formation as thermodynamically controlled reaction path, whereas kinetic control furnishes the corresponding phosphetes. Structural and luminescence properties of the rare class of phosphetes are explored, as well as for selected key intermediates.

Chalcogen-Transfer Rearrangement: Exploring Inter- versus Intramolecular P-P Bond Activation.

tert-Butyl-substituted diphospha[2]ferrocenophane has been used as a stereochemically confined diphosphane to explore the addition of O, S, Se and Te. Although the diphosphanylchalcogane has been obtained for tellurium, all other chalcogens give diphosphane monochalcogenides. The latter transform via chalcogen-transfer rearrangement to the corresponding diphosphanylchalcoganes upon heating. The kinetics of this rearrangement has been followed with NMR spectroscopy supported by DFT calculations. Intermediates during rearrangement point to a disproportionation/synproportionation mechanism for the S and Se derivatives. Cyclic voltammetry together with DFT studies indicate ferrocene-centred oxidation for most of the compounds presented.

A rigid anionic Janus bis(NHC) - new opportunities in NHC chemistry.

A phosphanido-type bridged bis(imidazolium) salt, readily prepared in two steps via reductive deselenization of a tricyclic 1,4-diphosphinine diselone, affords access to a novel anionic P-functional tricyclic bis(NHC) via deprotonation. The former also offers a P-functionalization/deprotonation sequence to access the first mixed P-substituted tricyclic bis(NHCs), as well as coordination of the phosphorus centers to rhodium(i) fragments.

2-(Dimethylamino)phosphinine: A Phosphorus-Containing Aniline Derivative.

The yet unknown 2-amino-substituted λ3 ,σ2 -phosphinines are phosphorus-containing aniline derivatives. Calculations show that the strong interaction of the π-donating NR2  group with the aromatic system results in a high π-density at the phosphorus atom. We could now synthesize 2-N(CH3 )2 -functionalized phosphinines, starting from a 3-N(CH3 )2 -substituted 2-pyrone and (CH3 )3 Si-C≡P. Their reaction with CuBr⋅S(CH3 )2 affords CuI  complexes with the first example of a neutral phosphinine acting as a rare bridging µ2 -P-4e donor-ligand between two CuI  centers. Our experimental and theoretical investigations show that 2-aminophosphinines are missing links in the series of known 2-donor-functionalized phosphinines.

Chalcogen-Transfer Rearrangement: Exploring Inter- versus Intramolecular P-P Bond Activation.

Invited for the cover of this issue are Rudolf Pietschnig and co-workers at the University of Kassel and Zsolt Kelemen at Budapest University of Technology and Economics. The image depicts Selene, the goddess of the moon in ancient Greek mythology, and the cycle of chalcogen-transfer rearrangement in the starry sky over the hills of the mountainous region of the northern shore of Lake Balaton (Mts. Badacsony and Gulács) in Hungary. Read the full text of the article at 10.1002/chem.202002481.