Characterizing the Distribution of a Stimulator of Interferon Genes Agonist and Its Metabolites in Mouse Liver by Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry.

A STING (stimulator of interferon genes) agonist GSK3996915 under investigation in early discovery for hepatitis B was orally dosed to a mouse model for understanding the parent drug distribution in liver, the target organ. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) was used to quantify the distribution of GSK3996915 in liver collected from mice administered a single oral dose at 90 mg/kg. GSK3996915 was detected with a zonal distribution localized in the portal triad and highly concentrated in the main bile ducts, indicating clearance through biliary excretion.

How Solid Surfaces Control Stability and Interactions of Supported Cationic Cu(dppf) Complexes─A Solid-State NMR Study.

Organometallic complexes are frequently deposited on solid surfaces, but little is known about how the resulting complex-solid interactions alter their properties. Here, a series of complexes of the type Cu(dppf)(L) (dppf = 1,1'-bis(diphenylphosphino)ferrocene, L = mono- and bidentate ligands) were synthesized, physisorbed, ion-exchanged, or covalently immobilized on solid surfaces and investigated by P MAS NMR spectroscopy. Complexes adsorbed on silica interacted weakly and were stable, while adsorption on acidic γ-AlO resulted in slow complex decomposition.

Cooperativity-Driven Reactivity of a Dinuclear Copper Dimethylglyoxime Complex.

In this report, we present the dinuclear copper(II) dimethylglyoxime (H dmg) complex [Cu (H dmg)(Hdmg)(dmg)] (1), which, in contrast to its mononuclear analogue [Cu(Hdmg) ] (2), is subject to a cooperativity-driven hydrolysis. The combined Lewis acidity of both copper centers increases the electrophilicity of the carbon atom in the bridging μ -O-N=C-group of H dmg and thus, facilitates the nucleophilic attack of H O. This hydrolysis yields butane-2,3-dione monoxime (3) and NH OH that, depending on the solvent, is then either oxidized or reduced.

Nonclinical Safety Assessment of Lipid Nanoparticle-and Emulsion-Based Self-Amplifying mRNA Vaccines in Rats.

Vaccines containing mRNA with the capacity to self-amplify represent an alternative to the mRNA vaccines that came to prominence during the COVID-19 pandemic. To gain further insights on the safety profile of self-amplifying mRNA- (SAM-) vaccines, this preclinical toxicology study in rats evaluated the effect of (i) the type of delivery system (lipid nanoparticle [LNP] vs cationic nano-emulsion [CNE]); (ii) antigen-encoding sequence (rabies glycoprotein G vs SARS-CoV-2 Spike); and (iii) RNA amplification. Further analyses also evaluated gene expression in peripheral blood after vaccination, and the biodistribution of vaccine RNA.

Crystalline Anions Based on Classical N-Heterocyclic Carbenes.

Herein, the first stable anions K[SIPr ] (4 a-K) and K[IPr ] (4 b-K) (SIPr =BpC{N(Dipp)CH } , IPr =BpC{N(Dipp)CH} ; Bp=4-PhC H ; Dipp=2,6-iPr C H ) derived from classical N-heterocyclic carbenes (NHCs) (i.e. SIPr and IPr) have been isolated as violet crystalline solids.

Caging of a Strongly Pairing Fluorescent Thymidine Analog with Soft Nucleophiles.

Controlling the pairing strength of nucleobases in DNA through reactions with compounds found inside the cell is a formidable challenge. Here we report how a thiazolyl substituent turns a strongly pairing ethynylpyridone C-nucleoside into a reactive residue in oligonucleotides. The thiazolyl-bearing pyridone reacts with soft nucleophiles, such as glutathione, but not with hard nucleophiles like hydroxide or carbonate.

Metal-metal communication between 1,1'-bis(diphenylphosphino)cobaltocenium and an organonickel moiety.

1,1'-Bis(diphenylphosphino)cobaltocenium (dppc), similar to 1,1'-bis(diphenylphosphino)ferrocene, can be coordinated by dicarbonylnickel(0) or cyclopentadienylnickel(II), respectively. The cyclic voltammogram of [Ni(CO)(dppc)] ([1]) showed two reversible reductions, at potentails nearly identical to (dppc). The ligand-based reductions were confirmed by IR spectroelectrochemistry (SEC), although the Δ was larger than might be expected if the ligand was electronically decoupled to the Ni(CO) moiety.

Mesoionic Imines (MIIs): Strong Donors and Versatile Ligands for Transition Metals and Main Group Substrates.

We report the synthesis and the reactivity of 1,2,3-triazolin-5-imine type mesoionic imines (MIIs). The MIIs are accessible by a base-mediated cycloaddition between a substituted acetonitrile and an aromatic azide, methylation by established routes and subsequent deprotonation. C=O-stretching frequencies in MII-CO and -Rh(CO) Cl complexes were used to determine the overall donor strength.

Synthesis and Characterization of Bidentate Isonitrile Iron Complexes.

The divalent iron complexes [FeBr(BINC)], [Cp*FeCl(BINC)] (Cp* = MeC), and [FeBr(CNArNC)] with the chelating bis(isonitrile) ligands BINC (bis(2-isocyanophenyl)phenylphosphonate) and CNArNC (2,2″-diisocyano-3,5,3″,5"tetramethyl-1,1':3',1″-terphenyl) have been prepared and characterized. Their subsequent reduction yields the di- and trinuclear compounds [Fe(BINC)], [Cp*Fe(BINC)], [Fe(CNArNC)], and [K(EtO)][Fe(CNArNC)]. The molecular structures of all new species were determined by X-ray crystallography and compared to those of related iron carbonyl complexes, demonstrating that the bidentate isonitrile ligands are capable surrogates for two CO ligands with only minimal distortion of the tetrahedral or octahedral geometry of the parent complexes.

[(η-Cymene)[3-(pyrid-2-yl)-1,2,4,5-tetrazine]chlororuthenium(II)], Redox Noninnocence and Dienophile Addition to Coordinated Tetrazine.

The bidentate ligand 3-(pyrid-2-yl)-1,2,4,5-tetrazine (TzPy) coordinated in the complex [CyRuCl(TzPy)]PF ([]; Cy = η--cymene) shows noninnocent behavior and can be modified through the addition of dienophiles, vinylferrocene (ViFc) or ethynylferrocene (EthFc). The kinetics and transition-state thermodynamic analysis of the reaction of [] + ViFc found Δ(298 K) = 67 kJ mol, while that of [] + EthFc was Δ(298 K) = 83 kJ mol. The room temperature second-order rate of [] + EthFc, = 1.

Electronic Structure of a Diiron Complex: A Multitechnique Experimental Study of [(dppf)Fe(CO) ].

Here we explore the electronic structure of the diiron complex [(dppf)Fe(CO)] [; dppf = 1,1'-bis(diphenylphosphino)ferrocene] in two oxidation states by an advanced multitechnique experimental approach. A combination of magnetic circular dichroism, X-ray absorption and emission, high-frequency electron paramagnetic resonance (EPR), and Mössbauer spectroscopies is used to establish that oxidation of occurs on the carbonyl iron ion, resulting in a low-spin iron(I) ion. It is shown that an unequivocal result is obtained by combining several methods.

Repeated Dose Toxicity Study and Developmental and Reproductive Toxicology Studies of a Respiratory Syncytial Virus Candidate Vaccine in Rabbits and Rats.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections, and vaccines are needed to treat young children and older adults. One of GSK's candidate vaccines for RSV contains recombinant RSVPreF3 protein maintained in the prefusion conformation. The differences in immune function of young children and older adults potentially require different vaccine approaches.

The core of the matter - arene substitution determines the coordination and catalytic behaviour of tris(1-phosphanyl-1'-ferrocenylene)arene gold(I) complexes.

Changing the aromatic core of C3-symmetric tris(ferrocenyl)arene-based tris-phosphanes has profound effects on their coordination behaviour towards gold(i). Depending on the arene (s-triazine, benzene, or trifluorobenzene), four different coordination modes can be distinguished and their preference has been rationalised using computational methods. The corresponding 1 : 1 ligand-to-metal complexes, studied by variable-temperature NMR spectroscopy, revealed fluctional behaviour in solution.

Tetrazine metallation boosts rate and regioselectivity of inverse electron demand Diels-Alder (iEDDA) addition of dienophiles.

Reported herein is the coordination of rhenium complexes to tetrazine ligand in [ReCl(CO)(TzPy)] [1] (TzPy = 3-(2-pyridyl)-1,2,4,5-tetrazine) and the rates of addition of different dienophiles to the tetrazine. Tetrazine coordiation lowers the ΔS contribution to ΔG for iEDDA addition.

Influence of Multisite Metal-Ligand Cooperativity on the Redox Activity of Noninnocent NS Ligands.

Metal-ligand cooperativity (MLC) relies on chemically reactive ligands to assist metals with small-molecule binding and activation, and it has facilitated unprecedented examples of catalysis with metal complexes. Despite growing interest in combining ligand-centered chemical and redox reactions for chemical transformations, there are few studies demonstrating how chemically engaging redox active ligands in MLC affects their electrochemical properties when bound to metals. Here we report stepwise changes in the redox activity of model Ru complexes as zero, one, and two BH molecules undergo MLC binding with a triaryl noninnocent NS ligand derived from -phenylenediamine ().

Tricoordinate Coinage Metal Complexes with a Redox-Active Tris-(Ferrocenyl)triazine Backbone Feature Triazine-Metal Interactions.

Invited for the cover of this issue is the group of Evamarie Hey-Hawkins at the University of Leipzig and colleagues at the University of Stuttgart and University of Regensburg. The image depicts the reported complexes as three similar flowers growing from one common branch representing the ligand. Read the full text of the article at 10.

Redox-inactive ions control the redox-activity of molecular vanadium oxides.

Polyoxometalates are key materials for energy conversion and storage due to their unique chemical tunability and electrochemical reactivity. Herein, we report that functionalization of molecular vanadium oxides, polyoxovanadates, with redox-inert Ca cations leads to a significant increase in their electron storage capabilities. The electrochemical performance of the Ca-functionalized dodecavanadate [CaVOCl(DMF)] (= ) was thus compared with that of the precursor compound (HNMe)[VOCl] (= ).

Nonclinical safety assessment of repeated administration and biodistribution of a novel rabies self-amplifying mRNA vaccine in rats.

The novel self-amplifying mRNA (SAM) technology for vaccines consists of an engineered replication-deficient alphavirus genome encoding an RNA-dependent RNA polymerase and the gene of the target antigen. To validate the concept, the rabies glycoprotein G was chosen as antigen. The delivery system for this vaccine was a cationic nanoemulsion.

Tricoordinate Coinage Metal Complexes with a Redox-Active Tris-(Ferrocenyl)triazine Backbone Feature Triazine-Metal Interactions.

2,4,6-Tris(1-diphenylphosphanyl-1'-ferrocenylene)-1,3,5-triazine (1) coordinates all three coinage metal(I) ions in a 1:1 tridentate coordination mode. The C -symmetric coordination in both solid state and solution is stabilised by an uncommon cation-π interaction between the triazine core and the metal cation. Intramolecular dynamic behaviour was observed by variable-temperature NMR spectroscopy.

(Benz-)imidazolin-2-ylidene-benzimidazolatonickel(II) Chelates: Syntheses, Structures, and Tuning of Noninnocent Chelate Ligand Behavior.

The deprotonation of 1-(1-benzimidazol-2-yl)-3-methylbenzimidazolium hexafluorophosphate (H[PF]) and 1-(1-benzimidazol-2-yl)-3-isopropylbenzimidazolium hexafluorophosphate (H[PF]) with potassium -butoxide in THF afforded the benzimidazolium-benzimidazolates H and H. The "instant carbene" behavior of these conjugated mesomeric betaines was demonstrated by trapping their carbenic tautomers H and H with elemental sulfur and selenium, which afforded the corresponding thio- and selenourea derivatives HE and HE (E = S, Se). The treatment of H and H with nickelocene furnished the nickel(II) complexes [NiCp()] and [NiCp()], which contain an anionic C,N-chelating NHC ligand.

Polyfunctional Imidazolium Aryloxide Betaine/Lewis Acid Catalysts as Tools for the Asymmetric Synthesis of Disfavored Diastereomers.

Enzymes are Nature's polyfunctional catalysts tailor-made for specific biochemical synthetic transformations, which often proceed with almost perfect stereocontrol. From a synthetic point of view, artificial catalysts usually offer the advantage of much broader substrate scopes, but stereocontrol is often inferior to that possible with natural enzymes. A particularly difficult synthetic task in asymmetric catalysis is to overwrite a pronounced preference for the formation of an inherently favored diastereomer; this requires a high level of stereocontrol.

Reply to Comment on Stabilization of Low-Valent Iron(I) in a High-Valent Vanadium(V) Oxide Cluster.

The authors of the Communication "Stabilization of Low-Valent Iron(I) in a High-Valent Vanadium(V) Oxide Cluster" reply to a Comment by Dr. Sproules, who offered an alternative interpretation of the metal oxidation states in the two electron reduced iron vanadate (NH Me )[(FeCl)V O Cl] .